Patent Publication Number: US-2023140802-A1

Title: Novel platforms for co-stimulation, novel car designs and other enhancements for adoptive cellular therapy

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a U.S. National Stage Application filed under 35 U.S.C. § 371 and claims priority to International Application No. PCT/US2018/053247, filed Sep. 27, 2018, which application claims priority under 35 U.S.C. § 119 to U.S. Provisional Application Ser. No. 62/564,249, filed Sep. 27, 2017, the disclosures of which are incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     Provided herein are novel costimulatory module and novel chimeric antigen receptors for adoptive cellular therapies of cancer, infection, allergic, degenerative and immune disorders. 
     INCORPORATION BY REFERENCE OF SEQUENCE LISTING 
     Accompanying this filing is a Sequence Listing entitled “Sequence ST25.txt”, created on Sep. 27, 2018 and having 60,347,260 bytes of data, machine formatted on IBM-PC, MS-Windows operating system. The sequence listing is hereby incorporated herein by reference in its entirety for all purposes. 
     BACKGROUND 
     Adoptive T-cell immunotherapy has risen to the forefront of treatment approaches for cancer. T cells can be engineered to express the genes of chimeric antigen receptors (CARs) that recognize tumor associated antigens. CARs are engineered immune-receptors, which can redirect T cells to selectively kill tumor cells. The general premise for their use in cancer immunotherapy is to rapidly generate tumor-targeted T cells, bypassing the barriers and incremental kinetics of active immunization and thereby act as ‘living drugs’. Unlike the physiologic T-cell receptor (TCR), which engages HLA-peptide complexes, CARs engage molecules that do not require peptide processing or HLA expression to be recognized. CARs therefore recognize antigen on any HLA background, in contrast to TCRs, which need to be matched to the haplotype of the patient. Furthermore, CARs can target tumor cells that have down-regulated HLA expression or proteasomal antigen processing, two mechanisms that contribute to tumor escape from TCR-mediated immunity. Another feature of the broad applicability of CARs is their ability to bind not only to proteins but also to carbohydrate and glycolipid structures, again expanding the range of potential targets. 
     SUMMARY 
     The disclosure provides an immune cell or immune cell population thereof expressing (i) at least one non-naturally occurring immune receptor and (ii) at least one non-naturally occurring agent that selectively activates the NF-κB signaling pathway. In one embodiment, the at least one non-naturally occurring immune receptor comprises at least one antigen-binding domain and at least one transmembrane domain. In another or a further embodiment, the at least one non-naturally occurring immune receptor is capable of recruiting at least one TCR associated signaling module. In another or a further embodiment, the at least one non-naturally occurring immune receptor is a chimeric antigen receptor (CAR) or a recombinant TCR. In another or a further embodiment, the at least one antigen-binding domain of the at least one non-naturally occurring immune receptor binds to an antigen selected from a group consisting of CD5; CD19; CD123; CD22; CD30; CD171; CS1 (also referred to as CD2 subset 1, CRACC, MPL, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TNF receptor family member B cell maturation (BCMass.); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMass.); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); Fms Like Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha (FRa or FR1); Folate receptor beta (FRb); Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CA1X); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDG1cp(1-1)Cer); transglutaminase 5 (TGSS); high molecular weight-melanoma associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WTI); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; survivin; telomerase; prostate carcinoma tumor antigen-1 (PCT A-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P4501B 1 (CYP1B 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAXS); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation Endproducts (RAGE-1); renal ubiquitous 1 (RU1); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRLS); and immunoglobulin lambda-like polypeptide 1 (IGLU), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBR1, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen); Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL11Rα, IL13Ra2, CD179b-IGLl1, TCRgamma-delta, NKG2D, CD32 (FCGR2A), Tn ag, Tim1-/HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Gonadotropin Hormone receptor (CGHR or GR), CCR4, GD3, SLAMF6, SLAMF4, HIV1 envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, KSHV K8.1, KSHV-gH, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), auto antibody to desmoglein 3 (Dsg3), auto antibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IgE, CD99, Ras G12V, Tissue Factor 1 (TF1), AFP, GPRCSD, Claudin18.2 (CLD18A2 or CLDN18A.2), P-glycoprotein, STEAP1, Livl, Nectin-4, Cripto, gpA33, BST1/CD157, low conductance chloride channel, and an antigen recognized by TNT antibody. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is selected from the group consisting of vFLIP K13, K13-opt, a NEMO mutant, a NEMO-fusion protein, IKK1-S176E-S180E, IKK2-S177E-S181E, RIP, IKKa, IKKγ, Tcl-1, MyD88-L265, any NF-κB activating protein or protein fragment, any inhibitor of an inhibitor of NF-κB pathway, any gene editing system capable of selectively activating NF-κB, any homolog or variant thereof and any combination thereof. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is of non-viral origin. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is a gene editing system. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway induces oligomerization of NEMO/IKKγ. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway induces activation of the IKK complex. In another or a further embodiment, at least one the non-naturally occurring agent capable of selectively activating NF-κB pathway does not activate the AKT pathway. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is expressed in a constitutive or inducible manner. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is expressed transiently. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is expressed stably. In another or a further embodiment, the activity of the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is controlled post-translationally through contacting the cell with a compound. In another or a further embodiment, the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is expressed as a fusion construct with one or more copies of a switch domain. In another or a further embodiment, the activity of the at least one non-naturally occurring agent capable of selectively activating NF-κB pathway is controlled at the post-translational level by administration of therapeutically effective amount of a compound that induces dimerization of the switch domain. In another or a further embodiment, the switch domain comprises one or more copies of a FKBP12 domain. In another or a further embodiment, the compound is AP20187 or Rimiducid or a homolog thereof. In another or a further embodiment, the immune cell is a T-lymphocyte (T-cell), a CAR-T cell, a TCR-expressing T cell, a tumor infiltrating lymphocyte (TIL), a tissue resident lymphocyte, a stem cell, an induced pluripotent stem cell or a Natural Killer (NK) cell. In another or a further embodiment, the immune cell has been engineered to lack a functional native T-Cell Receptor (TCR) signaling complex and/or (32 microglobulin. In another or a further embodiment, the at least one non-naturally occurring immune receptor and/or the at least one agent capable of selectively activating NF-κB signaling pathway are cloned into an endogenous TCR gene such that the expression of the at least one non-naturally occurring immune receptor and/or the at least one agent capable of selectively activating NF-κB signaling pathway are under control of the endogenous regulatory elements/promoter for the TCR gene. The disclosure also provides for the use of an immune cell or immune cell population as described herein that is used for the prevention and treatment of a disease selected from the group of a cancer, infectious disease, immune disease, and allergic disease. In another or a further embodiment, at least one polynucleotide encodes the at least one non-naturally occurring immune receptor and the at least one non-naturally occurring agent capable of selectively activating NF-κB signaling pathway are expressed from a single promoter. In another or a further embodiment, at least one polynucleotide encoding the at least one non-naturally occurring immune receptor and the at least one non-naturally occurring agent capable of selectively activating NF-κB signaling pathway are expressed using two or more separate promoters. In another or a further embodiment, the at least one polynucleotide comprises a first nucleic acid coding sequence encoding the at least one non-naturally occurring immune receptor separated from a second nucleic acid sequence encoding the non-naturally occurring agent capable of selectively activating NF-κB such that upon expression of the first and second nucleic acid coding sequences that non-naturally occurring immune receptor and non-naturally occurring agent capable of selectively activating NF-κB are not physically or chemically linked. In another or a further embodiment, the at least one non-naturally occurring immune receptor and/or the at least one non-naturally occurring agent capable of selectively activating NF-κB coding polynucleotide(s) are cloned into an endogenous TCR gene such that the at least one non-naturally occurring immune receptor and/or at least one non-naturally occurring agent capable of selectively activating NF-κB are under control of the endogenous regulatory elements/promoter for the TCR gene. In another or a further embodiment, one or more constant chains of the TCR genes are functionally re-expressed. 
     The disclosure also provides at least one recombinant polynucleotide encoding at least one non-naturally occurring immune receptor, the at least one recombinant polynucleotide comprising (a) a first nucleic acid domain encoding a partial or entire transmembrane and/or cytoplasmic domain and optionally the extracellular domain of an endogenous protein, wherein the endogenous protein is expressed on the surface of lymphocytes and triggers the activation and/or proliferation of the lymphocyte; (b) optionally a polynucleotide a linker; (c) a second nucleic acid domain operably linked to the first nucleic acid domain, wherein the second nucleic acid domain encodes one or more non-natural TCR antigen binding domain(s); (d) an optional third nucleic acid domain encoding a costimulatory domain; and (e) an optional additional nucleic acid domain encoding an accessory module. 
     The disclosure also provides at least one recombinant polynucleotide comprising a first nucleic acid encoding a non-naturally occurring immune receptor; and a second nucleic acid encoding an accessory module comprising a selective NF-κB activator. In one embodiment, the first nucleic acid and the second nucleic acid are separated by an oligonucleotide linker encoding a cleavable peptide linker. In another embodiment, the at least one comprises two recombinant polynucleotide such that the first nucleic acid and second nucleic acid are expressed from separate vectors. In another or a further embodiment, the selective NF-κB activator is a non-naturally occurring selective NF-κB activator. In another or a further embodiment, the non-naturally occurring immune receptor is selected from the group consisting of a CAR, an Ab-TCR, a TFP, a cTCR, a SIR and a recombinant TCR. In another or a further embodiment, the non-naturally occurring immune receptor comprises an (i) an extracellular antigen specific domain, (ii) a transmembrane domain, and (iii) an optional intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM), wherein (iii) is located at the C-terminus of the non-naturally occurring immune receptor. In another or a further embodiment, upon expression of the first and second nucleic acids sequences the non-naturally occurring immune receptor and selective NF-κB activator polypeptide are not physically or chemically linked. In another or a further embodiment, the extracellular antigen-specific domain binds to any one or more of CD5; CD19; CD123; CD22; CD30; CD171; CS1 (also referred to as CD2 subset 1, CRACC, MPL, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TNF receptor family member B cell maturation (BCMass.); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMass.); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); Fms Like Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha (FRa or FR1); Folate receptor beta (FRb); Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); AFP/MHC complex; epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CA1X); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDG1cp(1-1)Cer); transglutaminase 5 (TGS5); high molecular weight-melanoma associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WTI); WT1/MHC I complex; Cancer/testis antigen 1 (NY-ESO-1); NY-ESO-1/MHC I complex, Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; survivin; telomerase; prostate carcinoma tumor antigen-1 (PCT A-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P4501B 1 (CYP1B 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAXS); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation Endproducts (RAGE-1); renal ubiquitous 1 (RU1); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); HPV E6/MHC I complex; human papilloma virus E7 (HPV E7); HPV E7/MHC I complex; AFP/MHC I complex; Ras/MHC I complex; intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRD; Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRLS); and immunoglobulin lambda-like polypeptide 1 (IGLL1), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBR1, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen); Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL11Rα, IL13Ra2, CD179b-IGLl1, TCRgamma-delta, NKG2D, CD32 (FCGR2A), Tn ag, Tim1-/HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Gonadotropin Hormone receptor (CGHR or GR), CCR4, GD3, SLAMF6, SLAMF4, HIV1 envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, KSHV K8.1, KSHV-gH, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), auto antibody to desmoglein 3 (Dsg3), auto antibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IgE, CD99, Ras G12V, Tissue Factor 1 (TF1), AFP, GPRCSD, Claudin18.2 (CLD18A2 or CLDN18A.2), P-glycoprotein, STEAP1, Livl, Nectin-4, Cripto, gpA33, BST1/CD157, low conductance chloride channel, and an antigen recognized by TNT antibody. In another or a further embodiment, the selective NF-κB activator is selected from the group consisting of vFLIP K13, a NEMO mutant, a NEMO-fusion protein, IKK1-S176E-S180E, IKK2-S177E-S181E, RIP, FKBPx2-RIP-ID, IKK1, FKBPx2-IKKa, IKK2, FKBPx2-IKK2, Tcl-1, MyD88-L265, any NF-κB activating protein or protein fragment, any inhibitor of an inhibitor of NF-κB pathway, a gene editing system capable of selectively activating NF-κB, an RNA interference system that selectively activating NF-κB and any combination thereof. In another or a further embodiment, the selective NF-κB activator is expressed as a fusion construct with one or more copies of FKBP domain. In another or a further embodiment, the extracellular antigen specific domain is selected from the group consisting of: the variable region of the heavy chain (vH) of an antibody or a fragment thereof specific for a predefined target antigen; the variable region of the light chain (vL) of an antibody or a fragment thereof specific for a predefined target antigen; a single chain variable fragment (scFv) or a fragment thereof specific for a predefined target antigens; an antibody fragment (e.g., Fv, a Fab, a (Fab′)2) specific for a predefined target antigen; a single domain antibody (SDAB) fragments specific for a predefined target antigen; a camelid vHH domain specific for a predefined target antigen; a non-immunoglobulin antigen binding scaffolds specific for a predefined target antigen; a receptors specific or a fragment thereof for a predefined target antigen; a ligands or a fragment thereof specific for a predefined target antigen; a bispecific-antibody, -antibody fragment, -scFV, -vHH, -SDAB, -non-immunoglobulin antigen binding scaffold, -receptor or -ligand specific for one or more predefined target antigens; and an autoantigen or a fragment thereof. 
     The disclosure also provides at least one vector comprising the at least one polynucleotide of any of the foregoing polynucleotides constructs described herein and above. In one embodiment, the vector is selected from the group consisting of a DNA vector, an RNA vector, a plasmid, a lentivirus vector, adenoviral vector, AAV vector, a retrovirus vector, a baculovirus vector, a sleeping beauty transposon vector, and a piggybac transposon vector. 
     The disclosure also provides an immune effector cell or stem cell comprising at least one recombinant polynucleotide, construct or vector described herein and above. In one embodiment the immune cell is an antigen presenting cell. In another or a further embodiment, the immune effector cell is a human T cell, a human NKT cell or a synthetic T cell, NK cell, or a stem cell that can give rise to an immune effector cell, optionally, wherein the T cell is diaglycerol kinase (DGK) and/or Ikaros deficient and/or Brd4 deficient. 
     The disclosure also provides a method to (i) extend the life span of an immune cell expressing, (ii) stimulate proliferation of an immune cell, (iii) stimulate cytokine production by an immune cell, (iv) enhance antigen presentation by an immune cell, (v) protect an immune cell from apoptosis, the method comprising transfecting or transforming the immune cells with a polynucleotide encoding a selective NF-κB activator or a NF-κB specific stimulatory polypeptide. In one embodiment, the selective NF-κB activator or a NF-κB specific stimulatory polypeptide is selected from the group consisting of vFLIP K13, K13-opt, a NEMO mutant, a NEMO-fusion protein, IKK1-S176E-S180E, IKK2-S177E-S181E, RIP, IKKα, IKKβ, Tcl-1, MyD88-L265, any NF-κB activating protein or protein fragment, any inhibitor of an inhibitor of NF-κB pathway, any homolog or variant thereof and any combination thereof. In another or a further embodiment, the selective NF-κB activator or a NF-κB specific stimulatory polypeptide is expressed in a constitutive or inducible manner In another or a further embodiment, the selective NF-κB activator or a NF-κB specific stimulatory polypeptides controlled post-translationally through contacting the T cell with a compound. In another or a further embodiment, the selective NF-κB activator or a NF-κB specific stimulatory polypeptide is expressed as a fusion construct with one or more copies of FKBP domain. In another or a further embodiment, the activity of the selective NF-κB activator or a NF-κB specific stimulatory polypeptide is controlled at the post-translational level by administration of therapeutically effective amount of a compound that induces dimerization of the FKBP domain. In another or a further embodiment, the compound is AP20187 or rimiducid. 
     The disclosure also provides a method of making a non-naturally occurring immune receptor-expressing immune effector cell, comprising introducing at least one vector or at least one recombinant polynucleotide construct of the disclosure into an immune effector cell or a hematopoietic stem cell or progenitor cell that can give rise to an immune effector cell, under conditions such that a non-naturally occurring immune receptor is expressed and the immune effector cell comprises (i) extended life span, (ii) improved T cell proliferation, and/or (iii) reduced apoptosis compared to a CAR-T cell lacking an NFkB specific stimulatory polypeptide. In another or a further embodiment, the method further comprises providing a population of immune effector cells; and removing T regulatory cells from the population, thereby providing a population of T regulatory-depleted cells; wherein the steps are performed prior to introducing the vector or recombinant polynucleotide encoding the CAR and/or NFkB specific stimulatory polypeptide to the population. In another or a further embodiment, the T regulatory cells are removed from the cell population using an anti-CD25 antibody, or an anti-GITR antibody. In another or a further embodiment, the method further comprises a) providing a population of immune effector cells; and b) enriching P-glycoprotein (P-gp or Pgp; MDR1, ABCB1, CD243)-positive cells from the population, thereby providing a population of P-glycoprotein (P-gp or Pgp; MDR1, ABCB1, CD243)-enriched cells; wherein steps a) and b) are performed prior to or after introducing the vector or recombinant polynucleotide encoding the CAR and/or NFkB specific stimulatory polypeptide. In another or a further embodiment, the P-glycoprotein positive cells are enriched using any one or more of the methods selected from the group consisting of i) immunoselection using one or a cocktail of P-glycoprotein specific antibodies, ii) staining with one or more of fluorescent dyes that are substrates of P-glycoprotein, tetramethylrhodamine methyl ester (TMRM), Adriamycin and actinomycin-D) under conditions at which P-glycoprotein is active as a pump and enriching for cells that stain less with the dye, iii) selection of cells that are resistant to phototoxic compounds that are substrates of P-glycoprotein, such as any one or more of TH9402, 2-(4,5-dibromo-6-amino imino-3H-xanthen-9-yl)-benzoic acid methyl ester hydrochloride, 2-(4,5-dibromo-6-amino imino-3H-xanthen-9-yl)-benzoic acid ethyl ester hydrochloride, 2-(4,5-dibromo-6-amino imino-3H-xanthen-9-yl)-benzoic acid octyl ester hydrochloride, 2-(4,5-dibromo-6-amino imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride, 2-(6-ethyl amino-3-ethyl imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride, or derivatives thereof or combinations thereof, and iv) selection of cells that are resistant to cytotoxic compounds that are substrates of P-glycoprotein, such as vincristine, vinblastine, taxol, paclitaxel, mitoxantrone, etoposide, adriamycin, daunorubicin and actinomycin-D. 
     The disclosure also provide a method of generating a population of RNA-engineered cells comprising introducing in vitro transcribed RNA or RNAs or synthetic RNA or RNAs into a cell or population of cells, where the RNA or RNAs comprises a recombinant polynucleotide or polynucleotides of the disclosure. 
     The disclosure also provides a method of providing anti-disease immunity in a subject comprising administering to the subject an effective amount of the immune effector cell or a stem cell that can give rise to an immune effector cell of the disclosure, wherein the cell is an autologous T cell or an allogeneic T cell, or an autologous NKT cell or an allogeneic NKT cell or an autologous or an allogeneic hematopoietic stem cell or an autologous or an allogeneic iPSC that can give rise to an immune effector cell. In another or a further embodiment, the allogeneic T cell or allogeneic NKT cell or hematopoietic stem cell or iPSC lacks expression or has low expression of a functional TCR or a functional HLA. 
     The disclosure also provides a composition comprising an immune effector cell or a stem cell that can generate immune effector cells comprising a non-naturally occurring immune receptor and a selective NFkB activator, wherein the non-naturally occurring immune receptor comprises an antigen binding domains that bind to a disease-associated antigen associated said disease-associated antigen is selected from a group consisting of: CD5, CD19; CD123; CD22; CD30; CD171; CS-1 (also referred to as CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TNF receptor family member B cell maturation (BCMass.); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMass.); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); FmsLike Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha; Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CA1X); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); Fucosyl GM1; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDG1cp(1-1)Cer); transglutaminase 5 (TGSS); high molecular weight-melanomaassociated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; surviving; telomerase; prostate carcinoma tumor antigen-1 (PCT A-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P4501B 1 (CYP1B 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAXS); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation End products (RAGE-1); renal ubiquitous 1 (RU!); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRD; Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRLS); and immunoglobulin lambda-like polypeptide 1 (IGLU), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBR1, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen) Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL11Rα, IL13Ra2, CD179b-IGL11, ALK TCRgamma-delta, NKG2D, CD32 (FCGR2A), CSPG4-HMW-MAA, Tim1-/HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, VEGFR2/KDR, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Chorionic Gonadotropin Hormone receptor (CGHR), CCR4, SLAMF6, SLAMF4, HIV1 envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), KSHV-K8.1 protein, KSHV-gH protein, auto-antibody to desmoglein 3 (Dsg3), autoantibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IGE, CD99, RAS G12V, Tissue Factor 1 (TF1), AFP, GPRCSD, claudin18.2 (CLD18A2 OR CLDN18A.2)), P-glycoprotein, STEAP1, LIV1, NECTIN-4, CRIPTO, GPA33, BST1/CD157, low conductance chloride channel, and antigen recognized by TNT antibody. 
     The disclosure also provides a method of treating or preventing a disease associated with expression of a disease-associated antigen in a subject, comprising administering to the subject an effective amount of an immune effector cell comprising a non-naturally occurring immune receptor and a selective NFkB activator, wherein the non-naturally occurring immune receptor comprises an antigen binding domains that bind to a disease-associated antigen associated said disease-associated antigen is selected from a group consisting of: CD5, CD19; CD123; CD22; CD30; CD171; CS-1 (also referred to as CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TNF receptor family member B cell maturation (BCMass.); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMass.); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); FmsLike Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha; Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CA1X); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); Fucosyl GM1; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDG1cp(1-1)Cer); transglutaminase 5 (TGSS); high molecular weight-melanomaassociated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; surviving; telomerase; prostate carcinoma tumor antigen-1 (PCT A-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P4501B 1 (CYP1B 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAXS); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation End products (RAGE-1); renal ubiquitous 1 (RU1); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRD; Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRLS); and immunoglobulin lambda-like polypeptide 1 (IGLU), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBR1, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen) Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL11Rα, IL13Ra2, CD179b-IGLl1, ALK TCRgamma-delta, NKG2D, CD32 (FCGR2A), CSPG4-HMW-MAA, Tim1-/HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, VEGFR2/KDR, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Chorionic Gonadotropin Hormone receptor (CGHR), CCR4, SLAMF6, SLAMF4, HIV1 envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), KSHV-K8.1 protein, KSHV-gH protein, auto-antibody to desmoglein 3 (Dsg3), autoantibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IGE, CD99, RAS G12V, Tissue Factor 1 (TF1), AFP, GPRCSD, claudin18.2 (CLD18A2 OR CLDN18A.2)), P-glycoprotein, STEAP1, LIV1, NECTIN-4, CRIPTO, GPA33, BST1/CD157, low conductance chloride channel, and antigen recognized by TNT antibody, thereby treating the subject or preventing a disease in the subject. In another or a further embodiment, the disease associated with expression of the disease associated antigen is selected from the group consisting of a proliferative disease, a precancerous condition, a cancer, and a non-cancer related indication associated with expression of the disease-associated antigen. In another or a further embodiment, the cancer is a hematologic cancer chosen from one or more of chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt&#39;s lymphoma, diffuse large B cell lymphoma, primary effusion lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin&#39;s lymphoma, Hodgkin&#39;s lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, or pre-leukemia. In another or a further embodiment, the cancer is selected from the group consisting of colon cancer, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine, cancer of the esophagus, melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin&#39;s Disease, non-Hodgkin&#39;s lymphoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, solid tumors of childhood, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi&#39;s sarcoma, Merkel cell cancer, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers, combinations of said cancers, and metastatic lesions of said cancers. In another or a further embodiment, the disease is associated with infection by a virus including but not limited to HIV1, HIV2, HTLV1, Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus, adeno-associated virus, BK virus, Human Herpesvirus 6, Human Herpesvirus 8 influenza virus, parainfluenza virus, avian flu virus, MERS and SARS coronaviruses, Crimean Congo Hemorrhagic fever virus, rhino virus, enterovirus, Dengue virus, West Nile virus, Ebola virus, Marburg virus, Lassa fever virus, zika virus, RSV, measles virus, mumps virus, rhino virus, varicella virus, herpes simplex virus 1 and 2, varicella zoster virus, HIV-1, HTLV1, Hepatitis virus, enterovirus, hepatitis B virus, Hepatitis C virus, Nipah and Rift valley fever viruses, Japanese encephalitis virus, Merkel cell polyomavirus, or is associated with infection with mycobacterium tuberculosis, atypical mycobacteria species, Pneumocystis jirovecii, toxoplasmosis, rickettsia, nocardia, aspergillus, mucor, or candida. In another or a further embodiment, the disease is an immune or degenerative disease including but not limited to diabetes mellitus, multiple sclerosis, rheumatoid arthritis, pemphigus vulgaris, ankylosing spondylitis, Hoshimoto&#39;s thyroiditis, SLE, sarcoidosis, scleroderma, mixed connective tissue disease, graft versus host disease or Alzheimer&#39;s disease. 
     The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    depicts a cartoon of current an antibody, T-cell receptor (TCR), CAR and next generation CARs and SIRs. 
         FIG.  2    depicts a cartoon comparing second generation CAR biological activity and structure to an embodiment of the present disclosure depicting a CAR lacking CD28 or 41BB but expressing a NF-κB stimulatory molecule (NEMO and/or K13, or mutants thereof). 
         FIG.  3    shows strong activation of NF-κB by mNEMO-K270A, hNEMO-K277A and weak activation by hNEMO-K2771 and hNEMO-K277G mutant. 
         FIG.  4    shows activity of a Bispecific T cell engager targeting MPL and using a 161-scFv targeting domain. HEL-pLenti-hGluc and T cells were pre-incubated separately with the following supernatants at 4° C. for 2h Medium alone and pLenti-161-StreptagII-CD3-Myc-His-P02 (042517-P02-SC). Post-incubation, cells were co-cultured in U-bottom 96-well plate at an E:T ratio of 1:1 or 5:1 for 4h at 37 C. 50 μl of cells+sup/well were transferred to 384 well plate in triplicate. hGLuc assay was performed using 15 ul of CTZ assay buffer (1:100). 
         FIG.  5 A-C  shows CRISPR/Cas9-mediated TFP gene targeting into the TRAC locus and strategies to rescue TRAC expression. a, Top, TRAC locus with the 5′ end (grey) of the TRAC first exon, the TRAC gRNA (blue) and the corresponding PAM sequence (red). The two blue arrows indicate the predicted Cas9 double strand break. Bottom, CRISPR/Cas9-targeted integration into the TRAC locus. The targeting construct (AAV) contains a splice acceptor (SA), followed by a F2A coding sequence, the TFP gene and a polyA sequence, flanked by sequences homologous to the TRAC locus (LHA and RHA, left and right homology arm). Once integrated, the endogenous TCRα promoter drives TFP expression, while the TRAC locus is disrupted. B) The targeting construct expresses TFP and coexpresses TRAC (TCRα constant chain) through a 2A sequence. C) The targeting construct epresseses TFP and coexpresses via a 2A sequence a signal peptide which is in frame with the first exon present in the RHA so that TCRα promoter drives TFP expression as well as that of TRAC which is lacking the TCRα variable region (TRAV); TRAJ, TCRα joining region; 2A, the self-cleaving 2A sequence. pA: SV40/β-globin polyA sequence. 
         FIG.  6 A-E  shows various contruct designs for targeting cassette to direct an Ab-TCR to the TRAC locus. 
         FIG.  7 A-F  shows various contruct designs for targeting cassette to direct a cTCR (SIR) to TRAC locus. 
         FIG.  8 A-D  shows various contruct designs for targeting cassette to direct a cTCR (SIR) and a TCR to TRAC locus. 
         FIG.  9 A-D  shows various contruct designs for targeting cassette to direct a single chain cTCR (SIR) to TRAC locus. 
     
    
    
     DETAILED DESCRIPTION 
     Initial first-generation CARs were constructed through the fusion of a scFv (single chain fragment variable)-based antigen binding domain to an inert CD8 transmembrane domain, linked to a cytoplasmic signaling domain derived from the CD3- or Fc receptor y chains ( FIG.  1   ). 
     Although CD3-ζ chain aggregation is sufficient to enable lytic activity of T-cells, they failed to elicit a robust cytokine response, including interleukin-2 (IL-2), and support T-cell expansion upon repeated exposure to antigen. For optimal activation and proliferation, T cells require both T-cell receptor engagement and signaling, as well as costimulatory signaling through costimulatory receptors (i.e., CD28, 4-1BB, OX-40) on T cells binding to cognate ligands (i.e., CD80/86, 4-1BBL, OX-40L) expressed either by the targeted tumor cell or the antigen-presenting cells. To overcome the lack of T-cell co-stimulation, first generation CARs were further modified by incorporating the cytoplasmic signaling domains of T-cell costimulatory receptors. These second-generation CARs enhanced signaling strength and persistence of the modified T cells, leading to superior antitumor activity. Signaling through the costimulatory domains present in the 2nd generation CAR constructs results in activation of several signaling pathways, such as NF-κB and ERK. In particular, AKT activation promotes T cell activation but has been also shown to results in terminal differentiation, exhaustion and lack of persistence. 
       FIG.  2    depicts a cartoon of a 2 nd  generation CAR as described above next to a first generation CAR plus a specific NF-κB stimulatory molecule depicting the biological activity associated with each. 
     The CAR constructs in current clinical use are artificial in design as they represent fusion of several different proteins. In particular, inclusion of co-stimulatory domain in the 2 nd  generation CAR construct results in non-physiological signaling through the receptor, which in turn could contribute to their toxicity. Some CARs show tonic antigen-independent signaling, which leads to unrestrained cellular activation, eventually resulting in apoptosis, excessive cytokine release independent of cognate antigens, and immunologic exhaustion. Tonic signaling through co-stimulatory domains (e.g., 41BB and CD28 domain) has been shown to impede T cell survival. Thus, there is a need for improving the CAR design to achieve long term persistence of CAR modified T cells without the risk of excessive toxicity, such as cytokine release syndrome (CRS). 
     To overcome some of the design limitation of conventional 2 nd  generation CARs, several alternative designs, collectively termed next generation CARs, have been described, including Ab-TCR (WO 2017/070608 A1 incorporated herein by reference), TCR receptor fusion proteins or TFP (WO 2016/187349 A1 incorporated herein by reference), Synthetic Immune Receptors (SIRs) (see, WO 2018/102795 A1, incorporated herein by reference), Tri-functional T cell antigen coupler (Tri-TAC) (see, WO 2015/117229 A1, incorporated herein by reference). These alternative CAR designs, in general, lack a co-stimulatory domain. 
     To overcome the limitations of AKT activation and tonic signaling, this disclosure demonstrates the use of selective NF-κB activators, such as NEMO-mutants (e.g., hNEMO-K277A, hNEMO-K277A-DeltaV249-K255, mouse NEMO-K270A), K13-opt, IKK2-S177E-5181E, or IKK1-5176E-5180E, to provide costimulatory function. In contrast to 41BB- and CD28-derived costimulatory domains that activate a multitude of signaling pathways ( see,  2 nd  and 3 rd  generation CARs in  FIG.  1   ), selective NF-κB activators, such as, for example, hNEMO-K277A, hNEMO-K277A-DeltaV249-K255, mouse NEMO-K270A, K13-opt, IKK2-S177E-5181E, or IKK1-5176E-5180E, selectively activate the NF-κB pathway by activating the I-kappaB kinase (IKK) complex. The disclosure further describes an alternative non-naturally occurring immune receptor, e.g., CAR, design in which the costimulation is provided by an accessory module comprising a selective NF-κB activator that is co-expressed with the non-naturally occurring immune receptor (e.g., a CAR). However, in contrast to the 2 nd  generation CAR constructs in which the co-stimulatory domain is a component of the mature CAR polypeptide, the accessory module comprising the selective NF-κB activator is not necessarily an integral part of the mature immune receptor e.g., CAR, polypeptide. Such a design has advantage as it overcomes the problems of tonic signaling, excessive cytokine production and early exhaustion of T cells caused by the aggregation and non-physiological signaling through the costimulatory domains. The disclosure further provides a method to regulate the activity of the NF-κB activators by expressing them in fusion with switch domains, such as in fusion with tandem copies of a FKBP12v36 domain. 
     The disclosure demonstrates that expression of selective NF-κB activators, such, for example, as hNEMO-K277A, hNEMO-K277A-DeltaV249-K255, mouse NEMO-K270A, IKK2-S177E-S181E, IKK1-5176-5180E and K13-opt, in T cells extends their ability to proliferate long term in culture without undergoing senescence, thereby demonstrating for the first time that activation of a single pathway (i.e., NF-κB) is sufficient for postponing senescence of T cells. For example, CD19-CAR constructs co-expressing hNEMO-K277A or hNEMO-K277A-DeltaV249-K255 but lacking any costimulatory domain demonstrate superior in vivo efficacy as compared to 2nd generation CAR construct containing the 41BB costimulatory domain. The disclosure further demonstrates that selective activation of NF-κB is sufficient to promote the proliferation of T cells, delay senescence and improve the performance of T cells for adoptive cell therapy, including CAR-T cell therapy. Thus, the disclosure provides composition and methods to enhance the survival, proliferation, cytokine secretion, delay exhaustion and senescence and improve the in vivo expansion, persistence and anti-tumor activity of an immune cell, e.g., T cell, e.g., CAR-T or TCR-T or SIR-T cell, and/or an immune cell expressing a non-naturally occurring immune receptor, via selective or preferential (i.e., without AKT activation) activation of the NF-κB pathway in the immune cell. Moreover, the disclosure demonstrates that the use of selective NF-κB activators, such as, for example, hNEMO-K277A or hNEMO-K277A-DeltaV249-K255, is not limited to its use in CAR-T cells as they can be used in any T cell for adoptive cellular therapy, including T cells expressing endogenous TCR (e.g., tumor infiltrating lymphocytes), exogenous TCR, SIR and the like. 
     The disclosure further demonstrates that selective NF-κB activators, such as, for example, hNEMO-K277A, hNEMO-K277A-DeltaV249-K255, mouse NEMO-K270A, K13-opt, IKK2-S177E-5181E, or IKK1-5176E-5180E, can be used to improve the performance of vaccines by promoting cytokine secretion and antigen presentation by immune cells, e.g., antigen presenting cells, e.g., dendritic cells. For example, bone marrow derived dendritic cells (DC) expressing selective NF-κB activators, such as hNEMO-K277A, hNEMO-K277A-DeltaV249-K255, mouse NEMO-K270A, K13-opt, IKK2-5177E-5181E, or IKK1-5176E-5180E, show superior cytokine production, antigen presentation, and immune response (e.g., anti-tumor response or anti-infectious agent response) as compared to control DC. 
     The disclosure further provides NF-κB activators, including selective NF-κB activators that are of human origin and therefore are less immunogenic. 
     The disclosure further provides NF-κB activators, including selective NF-κB activators that can be expressed in the cytosol. The disclosure further provides NF-κB activators, including selective NF-κB activators, that are constitutively active and do not require a stimulus, e.g., treatment with a ligand, for their ability to activate NF-κB. 
     The disclosure futher provides several antigen binding domains that can be used in the generation of conventional CARs (e.g., 2nd generation CAR containing 41BB costimulatory domain) as well next generation CARs such as SIRs, zSIRs, Ab-TCR, and TFPs, for applications in adoptive cellular therapy. In some embodiments, these antigen binding domains are derived from antibodies and target antigens expressed in both hematologic malignancies and solid tumors. The SEQ ID Nos. of vL, vH and scFv fragments of these antigen binding domains are shown in Tables 6A-C. The SEQ ID Nos of the complementary determining regions (CDRs) of the light (vL) and heavy (vH) chains are shown in Tables 6A-B. The nucleic acid and amino acid SEQ IDs of exemplary 2nd generation CARs containing 41BB costimulatory domains and next generation CARs (e.g., zCAR-K13, zCAR-NEMO-K277A, SIRs, Ab-TCRs and TFP) based on these antigen binding domains are provided in Tables 10-14. The CARs containing these antigen binding domains show diverse in vitro and in vivo properties, such as binding affinity to the target antigens, cytokine secretion, proliferation, cyototoxicity, exhaustion, and long term persistence. As such, the non-naturally occurring immune receptors, e.g., CARs, containing these target antigens can be used to generate a diverse immune response. The polynucleotide, polypeptides, expression constructs, recombinantly engineered cells expressing CARs comprising the antigen binding domains of the disclosure, as well as method of making and using such polypeptides, polynucleotides and cells are described in methods known in the art and methods described in PCT/US2017/024843, WO 2014/160030 A2, WO 2016/187349 A1, WO 2017/070608 A1 and WO 2018/102795 A1, which are incorporated herein by reference in their entirety. The immune cells expressing the CARs comprising these antigen binding domains can be generated and used for adoptive cellular therapy of cancer, infectious and immune disorders using methods known in the art and methods described in WO 2017/070608 A1, WO 2016/187349 A1, WO 2018/102795 A1, WO 2015/117229 A1, which are incorporated herein by reference in their entirety. 
     The disclosure further provides novel methods for generating allogeneic T cells expressing TCR and CARs, including next generation CARs (e.g., TFP, SIR, Ab-TCR, cTCR), for the purpose of off-the-shelf adoptive cellular therapy. 
     The disclosure further provides novel methods of combination therapies using autologous and allogeneic T cells expressing TCR and CARs, including next generation CARs (e.g., TFP, SIR, Ab-TCR and cTCR. The disclosure provides methods of restoring the expresson and/or activity of TFPs based on CD3ε, CD3γ and CDδ chains in T cells lacking the expression of native TCRα, TCRβ, TCRγ or TCRδ chains by coexpressing in the cells expressing the TFPs the constant chains of TCRα, TCRβ, TCRγ or TCRδ. The disclosure further provides methods of restoring the expresson and/or activity of TFPs based on CD3E, CD3γ and CDδ chains in T cells lacking the expression of native TCRα, TCRβ, TCRγ or TCRδ chains by coexpressing in the cells expressing the TFPs either SIRs or Ab-TCR that cncode the full length or fragments of constant chains of TCRα, TCRβ, TCRγ or TCRδ. The disclosure provides that TFPs based on CD3ε, CD3γ and CDδ chains can be combined with SIRs or Ab-TCR encoding the constant chains of TCRα, TCRβ, TCRγ or TCRδ constant chains in T cells lacking the native TCRα, TCRβ, TCRγ or TCRδ chains for the purpose of allogeneic and off-the-shelf therapy. 
     As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and reference to “the polynucleotide” includes reference to one or more polynucleotides and so forth. 
     Also, the use of “or” means “and/or” unless stated otherwise. Similarly, “comprise,” “comprises,” “comprising” “include,” “includes,” and “including” are interchangeable and not intended to be limiting. 
     It is to be further understood that where descriptions of various embodiments use the term “comprising,” those skilled in the art would understand that in some specific instances, an embodiment can be alternatively described using language “consisting essentially of” or “consisting of” 
     Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Allen et al.,  Remington: The Science and Practice of Pharmacy  22 nd    ed ., Pharmaceutical Press (Sep. 15, 2012); Hornyak et al.,  Introduction to Nanoscience and Nanotechnology , CRC Press (2008); Singleton and Sainsbury,  Dictionary of Microbiology and Molecular Biology  3 rd    ed., revised ed ., J. Wiley &amp; Sons (New York, N.Y. 2006); Smith,  March&#39;s Advanced Organic Chemistry Reactions, Mechanisms and Structure  7 th    ed. , J. Wiley &amp; Sons (New York, N.Y. 2013); Singleton,  Dictionary of DNA and Genome Technology  3 rd    ed ., Wiley-Blackwell (Nov. 28, 2012); and Green and Sambrook,  Molecular Cloning: A Laboratory Manual  4 th ed ., Cold Spring Harbor Laboratory Press (Cold Spring Harbor, N.Y. 2012), provide one skilled in the art with a general guide to many of the terms used in the present application. For references on how to prepare antibodies, see Greenfield,  Antibodies A Laboratory Manual  2 nd  ed., Cold Spring Harbor Press (Cold Spring Harbor N.Y., 2013); Köhler and Milstein,  Derivation of specific antibody - producing tissue culture and tumor lines by cell fusion , Eur. J. Immunol. 1976 Jul. 6(7):511-9; Queen and Selick,  Humanized immunoglobulins , U.S. Pat. No. 5,585,089 (1996 December); and Riechmann et al.,  Reshaping human antibodies for therapy , Nature 1988 Mar 24, 332(6162):323-7A11 headings and subheading provided herein are solely for ease of reading and should not be construed to limit the invention. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and specific examples are illustrative only and not intended to be limiting. 
     All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. Any references cited are not an admission that any of the information provided therein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art. 
     The term “about” when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20% or in some instances ±10%, or in some instances ±5%, or in some instances ±1%, or in some instances ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods or describe the compositions herein. Moreover, any value or range (e.g., less than 20 or similar terminology) explicitly includes any integer between such values or up to the value. Thus, for example, “one to five mutations” explicitly includes 1, 2, 3, 4, and/or 5 mutations. 
     The term “Ab-TCR” or “AbTCR” refers to a next generation CAR platform as described in WO 2017/070608 A1 which is incorporated herein by reference. In an embodiment, an Ab-TCR comprises an antibody moiety that specifically binds to a target antigen fused to a TCR module capable of recruiting at least one TCR signaling module. Exemplary TCR modules that can be used in the construction of Ab-TCR are provided in SEQ ID NO: 959-964 (Table 6D) and in WO 2017/070608 A1 which is incorporated herein by reference. In the TCR module TCRb-IAH-6MD three amino acid residues (F133, E136 and Q139) found in human TCRb chain (SEQ ID NO: 15053) (see Tables 4, 5 &amp; 6D) are mutated to the residues Isoleucine, Alanine, and Histidine found in the murine TCRb chain, respectively, so as to enhance the expression of this module. Similarly, in the TCR module IgGl-CH1-TCRa-SDVP-6MD four amino acid residues (P91, E92, S93, S94) found in human TCRα chain (SEQ ID NO: 15041) are mutated to the residues S, D, V, P found in the murine TCRα chain so as to enhance the expression of this module (see Tables 3 &amp; 6D). Exemplary Ab-TCRs co-expressing an accessory module encoding NEMO-K277A are provided in SEQ ID NO: 3124-3523 (Table 14). However, the accessory module encoding NEMO-K277A is optional. Ab-TCR with the antigen binding domains (i.e., vL and vH fragments, ligands and receptors etc.) described in this disclosure can be constructed without NEMO-K277A. As such this accessory module along with the upstream Furine-SGSG-F2A sequence can be deleted from the Ab-TCR. Alternatively, the accessory module encoding NEMO-K277A can be replaced by accessory modules encoding other proteins, such as hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, or IKK1-5176E-5180E, and MyD88-L265P, FKBPx2-NEMO, NEMO-L600-FKBPx2 etc. Furthermore, the TCR modules present in the Ab-TCR can be substituted by other TCR modules described in WO 2017/070608 Al. For example, the Ab-TCR represented by SEQ ID NO: 3124-3323 contain TCR modules IgCL-TCRb-IAH-6MD (SEQ ID NO: 960) and IgGl-CH1-TCRa-SDVP-6MD (SEQ ID NO: 963) which can be substituted by TCR modules IgCL-TCRb-wt2-opt-6MD (SEQ ID NO: 961) and IgGl-CH1-TCRa-wt2-opt-6MD (SEQ ID NO: 964), resepectively. Exemplary Ab-TCRs co-expressing an accessory module encoding NEMO-K277A and containing the TCR modules IgCL-TCRg-6MD (SEQ ID NO: 959) and IgGl-CH1-TCRd-6MD (SEQ ID NO: 962) are provided in SEQ ID NO: 3324-3523. The order of the antigen binding domains in these constructs is the same as the order of the constructs shown in Table 14 and therefore a Ab-TCR based on IgCL-TCRg-6MD (SEQ ID NO: 959) and IgGl-CH1-TCRd-6MD (SEQ ID NO: 962) targeting a particular antigen and containing a specific antigen binding domain can be identified by referring to Table 14. 
     The term “accessory module” refers to any one or more of hNEMO-K277A (or NEMO-K277A), hNEMO-K277A-delta-V249-K555, mNEMO-K270A, K13-opt, IKK2-5177E-S181E (or IKK2-SS/EE), IKKl-5176E-5180E (or IKKl-SS/EE), MyD88-L265P, TCL-la, MTCP-1, CMV-141, 41BBL, CD4OL, vFLIP-K13, MC159, cFLIP-L/MRITa, cFLIP-p22, HTLV1 Tax, HTLV2 Tax, HTLV2 Tax-RS mutant, FKBPx2-K13, FKBPx2-HTLV2-Tax, FKBPx2-HTLV2-Tax-RS, IL6R-304-vHH-Alb8-vHH, IL12f, PD1-4H1 scFV, PD1-5C4 scFV, PD1-4H1-A1b8-vHH, PD1-5C4-A1b8-vHH, CTLA4-Ipilimumab-scFv, CTLA4-Ipilimumab-Alb8-vHH, IL6-19A-scFV, IL6-19A-scFV-A1b8-vHH, sHVEM, sHVEM-Alb8-vHH, hTERT, Fx06, shRNA targeting Brd4, IgSP-[TRAC-opt2], IgSP-R[TRBC-opt2] and combination thereof that is expressed in an immune cell (e.g., T cell, e.g., CAR-T cell or TCR-T cell) to decrease, regulate or modify the activity of the immune cell. In some embodiments, the accessory module is co-expressed with an immune receptor such as a CAR or a TCR to increase, decrease, regulate or modify the expression or activity of a CAR or a TCR or a CAR-expressing or a TCR-expressing cell. The accessory module can be co-expressed with a CAR or a TCR using a single vector or using two or more different vectors. In a further embodiment, the accessory module comprises an FKBP (FK506 binding protein)-fusion protein, such as FKBPx2-NEMO, whose activity can be controlled by the administration of a dimerizer molecule. In some embodiments, the accessory module is expressed in an antigen presenting cell, e.g., a dendritic cell. 
     As used herein “affinity” is meant to describe a measure of binding strength. Affinity, in some instances, depends on the closeness of stereochemical fit between a binding agent and its target (e.g., between an antibody and antigen including epitopes specific for the binding domain), on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. Affinity generally refers to the “ability” of the binding agent to bind its target. There are numerous ways used in the art to measure “affinity”. For example, methods for calculating the affinity of an antibody for an antigen are known in the art, including use of binding experiments to calculate affinity. Binding affinity may be determined using various techniques known in the art, for example, surface plasmon resonance, bio-layer interferometry, dual polarization interferometry, static light scattering, dynamic light scattering, isothermal titration calorimetry, ELISA, analytical ultracentrifugation, and flow cytometry. An exemplary method for determining binding affinity employs surface plasmon resonance. Surface plasmon resonance is an optical phenomenon that allows for the analysis of real-time biospecific interactions by detection of alterations in protein concentrations within a biosensor matrix, for example using the BlAcore system (Pharmacia Biosensor AB, Uppsala, Sweden and Piscataway, N.J.). As used herein, the term “specific binding” means the contact between an antibody and an antigen with a binding affinity of at least 10 −6  M. In certain aspects, antibodies bind with affinities of at least about 10′M, and preferably 10 −8  M, 10 −9  M, 10 −10  10 −11 M, or 10 −12 M. 
     The “AKT Pathway” or “PI3K-AKT Pathway” as used herein is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K (phosphatidylinositol 3-kinase) and Akt (Protein Kinase B). 
     The term “antibody,” as used herein, refers to a protein, or polypeptide sequence derived from an immunoglobulin molecule which specifically binds with an antigen. Antibodies can be monoclonal, or polyclonal, multiple or single chain, or intact immunoglobulins, and may be derived from natural sources or from recombinant sources. Antibodies can be tetramers of immunoglobulin molecules. The antibody may be ‘humanized’, ‘chimeric’ or non-human. 
     The term “antibody fragment” refers to at least one portion of an antibody, that retains the ability to specifically interact with (e.g., by binding, steric hindrance, stabilizing/destabilizing, spatial distribution) an epitope of an antigen. Examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′h, Fv fragments, scFv antibody fragments, disulfide-linked Fvs (sdFv), a Fd fragment consisting of the VH and CH1 domains, linear antibodies, single domain antibodies (sdAb) such as either vL or vH, camelid vHH domains, multi-specific antibodies formed from antibody fragments such as a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region, and an isolated CDR or other epitope binding fragments of an antibody. An antigen binding fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (see, e.g., Hollinger and Hudson, Nature Biotechnology 23:1126-1136, 2005). Antigen binding fragments can also be grafted into scaffolds based on polypeptides such as a fibronectin type III (Fn3) (see U.S. Pat. No. 6,703,199, which describes fibronectin polypeptide mini-bodies). 
     The term “antibody heavy chain,” refers to the larger of the two types of polypeptide chains present in antibody molecules in their naturally occurring conformations, and which normally determines the class to which the antibody belongs. 
     The term “antibody light chain,” refers to the smaller of the two types of polypeptide chains present in antibody molecules in their naturally occurring conformations. Kappa (κ) and lambda (2) light chains refer to the two major antibody light chain isotypes. 
     “Anticancer agent” refers to agents that inhibit aberrant cellular division and growth, inhibit migration of neoplastic cells, inhibit invasiveness or prevent cancer growth and metastasis. The term includes chemotherapeutic agents, biological agent (e.g., siRNA, viral vectors such as engineered MLV, adenoviruses, herpes virus that deliver cytotoxic genes), antibodies and the like. 
     The term “anticancer effect” refers to a biological effect which can be manifested by various means, including but not limited to, a decrease in tumor volume, a decrease in the number of cancer cells, a decrease in the number of metastases, an increase in life expectancy, decrease in cancer cell proliferation, decrease in cancer cell survival, or amelioration of various physiological symptoms associated with the cancerous condition. An “anticancer effect” can also be manifested by the ability of the CARs in prevention of the occurrence of cancer in the first place. 
     The term “antigen” or “Ag” refers to a molecule that provokes an immune response. This immune response may involve either antibody production, or the activation of specific immunologically-competent cells, or both. The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which comprises a nucleotide sequences or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an “antigen” as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full length nucleotide sequence of a gene. The disclosure includes, but is not limited to, the use of partial nucleotide sequences of more than one gene and that these nucleotide sequences are arranged in various combinations to encode polypeptides that elicit the desired immune response. Moreover, a skilled artisan will understand that an antigen need not be encoded by a “gene” at all. It is readily apparent that an antigen can be generated synthesized or can be derived from a biological sample, or might be macromolecule besides a polypeptide. Such a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a fluid with other biological components. 
     Non-limiting examples of target antigens include: CD5; CD19; CD123; CD22; CD30; CD171; CS1 (also referred to as CD2 subset 1, CRACC, MPL, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TNF receptor family member B cell maturation (BCMass.); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMass.); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); Fms Like Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha (FRa or FR1); Folate receptor beta (FRb); Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CA1X); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDG1cp(1-1)Cer); transglutaminase 5 (TGSS); high molecular weight-melanoma associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; survivin; telomerase; prostate carcinoma tumor antigen-1 (PCT A-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P4501B 1 (CYP1B 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAXS); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation Endproducts (RAGE-1); renal ubiquitous 1 (RU1); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRD; Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRLS); and immunoglobulin lambda-like polypeptide 1 (IGLLl), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBR1, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen); Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL11Rα, IL13Ra2, CD179b-IGL11, TCRgamma-delta, NKG2D, CD32 (FCGR2A), Tn ag, Tim1-/HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Gonadotropin Hormone receptor (CGHR or GR), CCR4, GD3, SLAMF6, SLAMF4, HIV1 envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, KSHV K8.1, KSHV-gH, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), auto antibody to desmoglein 3 (Dsg3), auto antibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IgE, CD99, Ras G12V, Tissue Factor 1 (TF1), AFP, GPRCSD, Claudin18.2 (CLD18A2 or CLDN18A.2), P-glycoprotein, STEAP1, Livl, Nectin-4, Cripto, gpA33, BST1/CD157, low conductance chloride channel, and the antigen recognized by TNT antibody. 
     The term “antigen presenting cell” or “APC” refers to an immune system cell such as an accessory cell (e.g., a B-cell, a dendritic cell, and the like) that displays a foreign antigen complexed with major histocompatibility complexes (MHC&#39;s) on its surface. T-cells may recognize these complexes using their T-cell receptors (TCRs). APCs process antigens and present them to T-cells. 
     The term “anti-infection effect” refers to a biological effect which can be manifested by various means, including but not limited to, e.g., decrease in the titer of the infectious agent, a decrease in colony counts of the infectious agent, amelioration of various physiological symptoms associated with the infectious condition. An “anti-infectious effect” can also be manifested by the ability of the peptides, polynucleotides, cells and antibodies in prevention of the occurrence of infection in the first place. 
     The term “antitumor effect” or “anti-cancer effect” refers to a biological effect which can be manifested by various means, including but not limited to, e.g., a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in tumor cell proliferation, or a decrease in tumor cell survival. 
     An “antigen binding domain” or “antigen binding module” or “antigen binding segment” or “antigen specific domain” (ASD) refers to a polypeptide or peptide that due to its primary, secondary or tertiary sequence, post-translational modifications and/or charge binds to an antigen with a high degree of specificity. The antigen binding domain may be derived from different sources, for example, an antibody (full length heavy chain, Fab fragments, single chain Fv (scFv) fragments, divalent single chain antibodies or diabodies), a non-immunoglobulin binding protein, a ligand or a receptor. There are, however, numerous alternatives, such as linked cytokines (which leads to recognition of cells bearing the cytokine receptor), affibodies, ligand binding domains from naturally occurring receptors, soluble protein/peptide ligand for a receptor (for example on a tumor cell), peptides, and vaccines to prompt an immune response, which may each be used in various embodiments of the invention. In some embodiments, almost any molecule that binds a given antigen with high affinity can be used as an ASD, as will be appreciated by those of skill in the art. In some embodiments, the antigen binding domain comprises T cell receptors (TCRs) or portions thereof. In exemplary embodiments, nucleic acids encoding antigen binding domains comprising scFVs are set forth herein in SEQ ID NOs: 642-902 and in Table 6C. In exemplary embodiments, amino acids encoding antigen binding domains comprising scFVs are set forth herein in SEQ ID NOs: 4555-4815 in Table 6C. 
     The term “Association constant (Ka)” is defined as the equilibrium constant of the association of a receptor and ligand. 
     “Autoantibody” refers to an antibody that is produced by a B-cell specific for an autoantigen. 
     The term “autoantigen” refers to an endogenous antigen that stimulates production of an autoimmune response, such as production of autoantibodies. Autoantigen also includes a self-antigen or antigen from a normal tissue that is the target of a cell mediated or an antibody-mediated immune response that may result in the development of an autoimmune disease. Examples of autoantigens include, but are not limited to, desmoglein 1, desmoglein 3, and fragments thereof. 
     “Avidity” refers to the strength of the interaction between a binding agent and its target (e.g., the strength of the interaction between an antibody and its antigen target, a receptor and its cognate and the like). The avidity can be weak or strong. Methods for calculating the affinity of an antibody for an antigen are known in the art, including use of binding experiments to calculate affinity. Antibody activity in functional assays (e.g., flow cytometry assay) is also reflective of antibody affinity. Antibodies and affinities can be phenotypically characterized and compared using functional assays (e.g., flow cytometry assay). 
     As used herein, the term “backbone” refers to the specific combination of CARs (Table 1) and accessory modules as described in Table 2. In exemplary embodiments, specific combinations of CARs and accessory modules which comprise various backbones are described in Table 2. In one embodiment, the CAR and the accessory module are encoded by a single nucleic acid molecule. In another embodiment, the CAR is encoded by the first nucleic acid molecule and the accessory module is encoded by a second nucleic acid molecule. In some embodiments, the accessory module is encoded by more than one nucleic acid molecule, depending on the number of components in the accessory modules. 
     As used herein “beneficial results” may include, but are in no way limited to, lessening or alleviating the severity of the disease condition, preventing the disease condition from worsening, curing the disease condition, preventing the disease condition from developing, lowering the chances of a patient developing the disease condition and prolonging a patient&#39;s life or life expectancy. As non-limiting examples, “beneficial results” or “desired results” may be alleviation of one or more symptom(s), diminishment of extent of the deficit, stabilized (i.e., not worsening) state of cancer progression, delay or slowing of metastasis or invasiveness, and amelioration or palliation of symptoms associated with the cancer. 
     As used herein, the term “binding domain” or “antibody molecule” refers to a protein, e.g., an immunoglobulin chain or fragment thereof, ligand domain or fragment thereof (as the case may be), comprising at least one domain, e.g., immunoglobulin variable domain sequence that can bind to a target with affinity higher than a non-specific domain. The term encompasses antibodies and antibody fragments, or ligands and ligand fragments. In another embodiment, an antibody molecule is a multispecific antibody molecule, e.g., it comprises a plurality of immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence of the plurality has binding specificity for a first epitope and a second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope. In another embodiment, a multispecific antibody molecule is a bispecific antibody molecule. A bispecific antibody has specificity for two antigens. A bispecific antibody molecule is characterized by a first immunoglobulin variable domain sequence which has binding specificity for a first epitope and a second immunoglobulin variable domain sequence that has binding specificity for a second epitope. A bispecific molecule may be a bispecific T cell engaging antibody in which first antigen binding domain binds to an antigen (e.g., CD3c) expressed on T cells and the second antigen binding domain binds to an antigen expressed on a disease causing or disease associated cell (e.g., a cancer cell). The bispecific antibodies can be used for inducing T cell mediated cytotoxicity against cells expressing the target antigen recognized by their second antigen binding domain. The antigen binding domains described in this disclosure can be used to construct bispecific T cell engagers. The nucleic acid sequences of exemplary bispecific T cell engagers comprising the antigen binding domains (e.g. scFv) described in this disclosure are presented in SEQ ID NO: 3545-3830 (Table 13). The corresponding amino acid sequences are presented in SEQ ID NO: 7458-7721. 
     “Binds the same epitope as” means the ability of an antibody, scFv, or other antigen binding domain to bind to a target antigen and having the same epitope as an exemplified antibody, scFv, or other antigen binding domain. As an example, the epitopes of the exemplified antibody, scFv, or other binding agent and other antibodies can be determined using standard epitope mapping techniques. Epitope mapping techniques, well known in the art include Epitope Mapping Protocols in Methods in Molecular Biology, Vol. 66 (Glenn E. Morris, Ed., 1996) Humana Press, Totowa, N.J. For example, linear epitopes may be determined by, e.g., concurrently synthesizing large numbers of peptides on solid supports, the peptides corresponding to portions of the protein molecule, and reacting the peptides with antibodies while the peptides are still attached to the supports. Such techniques are known in the art and described in, e.g., U.S. Pat. No. 4,708,871; Geysen et al, (1984) Proc. Natl. Acad. Sci. USA 8:3998-4002; Geysen et al, (1985) Proc. Natl. Acad. Sci. USA 82:78-182; Geysen et al, (1986) Mol. lmmunol. 23: 709-715. The epitope bound by the antigen binding domain of a CAR can be also determined by the Epitope Binning assay. Epitope binning is a competitive immunoassay used to characterize and then sort a library of monoclonal antibodies against a target protein. Antibodies against a similar target are tested against all other antibodies in the library in a pairwise fashion to see if antibodies block one another&#39;s binding to the epitope of an antigen. After each antibody has a profile created against all of the other antibodies in the library, a competitive blocking profile is created for each antibody relative to the others in the library. Closely related binning profiles indicate that the antibodies have the same or a closely related epitope and are “binned” together. Similarly, conformational epitopes are readily identified by determining spatial conformation of amino acids such as by, e.g., hydrogen/deuterium exchange, x-ray crystallography and two-dimensional nuclear magnetic resonance. See, e.g., Epitope Mapping Protocols, supra. Antigenic regions of proteins can also be identified using standard antigenicity and hydropathy plots, such as those calculated using, e.g., the Omiga version 1.0 software program available from the Oxford Molecular Group. This computer program employs the Hopp/Woods method, Hopp et al, (1981) Proc. Natl. Acad. Sci USA 78:3824-3828; for determining antigenicity profiles, and the Kyte-Doolittle technique, Kyte et al, (1982) J.Mol. Bioi. 157: 1 05-132; for hydropathy plots. To determine if selected monoclonal antibodies against a target (e.g., CD19) bind to unique epitopes, each antibody can be biotinylated using commercially available reagents (Pierce, Rockford, Ill.). Competition studies using unlabeled monoclonal antibodies and biotinylated monoclonal antibodies can be performed using CD19-extracellualr domain coated-ELISA plates. Biotinylated mAb binding can be detected with a strep-avidin-alkaline phosphatase probe. Exemplary epitopes of human CD20 antigen bound by scFv and CARs of the current disclosure are provided in SEQ ID NO: 15149-15154. Exemplary epitopes of human BCMA bound by scFv and CARs of the current disclosure are provided in SEQ ID NO: 15155-15159. An exemplary epitope of human MPL antigen bound by scFv and CARs of the current disclosure is provided in SEQ ID NO: 15160. 
     As used herein, the term “biological equivalent thereof” is intended to be synonymous with “equivalent thereof” when referring to a reference protein, antibody or fragment thereof, polypeptide or nucleic acid, intends those having minimal homology while still maintaining desired structure or functionality. Unless specifically recited herein, it is contemplated that any of the above also includes equivalents thereof. For example, an equivalent intends at least about 70% homology or identity, or at least 80% homology or identity and alternatively, or at least about 85%, or alternatively at least about 90%, or alternatively at least about 95%, or alternatively at least 98% percent homology or identity and exhibits substantially equivalent biological activity to the reference protein, polypeptide, antibody or fragment thereof or nucleic acid. Alternatively, when referring to polynucleotides, an equivalent thereof is a polynucleotide that hybridizes under stringent conditions to the reference polynucleotide or its complement. Alternatively, when referring to polypeptides or proteins, an equivalent thereof is an expressed polypeptide or protein from a polynucleotide that hybridizes under stringent conditions to the polynucleotide or its complement that encodes the reference polypeptide or protein. 
     As used herein, the term “CDR” or “complementarity determining region” is intended to mean the non-contiguous antigen combining sites found within the variable region of both heavy and light chain polypeptides. These particular regions have been described by Kabat et al., J. Bioi. Chem. 252:6609-6616 (1977); Kabat et al., U.S. Dept. of Health and Human Services, “Sequences of proteins of immunological interest” (1991); Chothia et al., J. Mol. Bioi. 196:901-917 (1987); and MacCallum et al., J. Mol. Bioi. 25 262:732-745 (1996), where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or grafted antibodies or variants thereof is intended to be within the scope of the term as defined and used herein. As used herein, the different CDRs of an antibody could be also defined by a combination of the different definitions. For example, vHCDR1 could be defined based on Kabat and VHCDR2 could be defined based on Chothia. The amino acid residues which encompass the CDRs as defined by each of the above cited references are as follows: 
     
       
         
           
               
               
            
               
                   
               
               
                   
                 CDR DEFINITIONS 
               
            
           
           
               
               
               
               
            
               
                   
                 Kabat 
                 Chothia 
                 MacCallum 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 VHCDR1 
                 31-35 
                 26-32 
                 30-35 
               
               
                   
                 VHCDR2 
                 50-65 
                 53-55 
                 47-58 
               
               
                   
                 VHCDR3 
                  95-102 
                 96-10 
                 193-101 
               
               
                   
                 VLCDR1 
                 24-34 
                 26-32 
                 30-36 
               
               
                   
                 VLCDR2 
                 50-56 
                 50-52 
                 46-55 
               
               
                   
                 VLCDR3 
                 89-97 
                 91-96 
                 89-96 
               
               
                   
               
               
                 (Residue Numbers correspond to the identified reference). 
               
            
           
         
       
     
     The SEQ IDs of the CDRs of the different vL and vH segments that can make up antigen binding domains of CARs of the disclosure are provided in SEQ ID NO: 13204-14121 and SEQ ID NO: 14122-15039, respectively (Tables 6A, B) and in Tables 5-6 in PCT/US2017/064379, which are incorporated herein by reference,. 
     In some embodiments, reference to an antigen-binding module (such as a Fab-like or Fv-like antigen-binding module) that specifically binds to a target antigen means that the antigen-binding module binds to the target antigen with (a) an affinity that is at least about 10 (e.g., about 10, 20, 30, 40, 50, 75, 100, 200, 300, 400, 500, 750, 1000 or more) times its binding affinity for other molecules; or (b) a K d  no more than about 1/10 (e.g., 1/10, 1/20, 1/30, 1/40, 1/50, 1175, 1/100, 1/200, 1/300, 1/400, 1/500, 1/750, 1/1000 or less) times its K d  for binding to other molecules. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis, or radioimmunoprecipitation assay (RIA). Ka can be determined by methods known in the art, such as surface plasmon resonance (SPR) assay utilizing, for example, Biacore instruments, or kinetic exclusion assay (KinExA) utilizing, for example, Sapidyne instruments. 
     “Cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer include, but are not limited to B-cell lymphomas (Hodgkin&#39;s lymphomas and/or non-Hodgkins lymphomas), T cell lymphomas, myeloma, myelodysplastic syndrome, skin cancer, brain tumor, breast cancer, colon cancer, rectal cancer, esophageal cancer, anal cancer, cancer of unknown primary site, endocrine cancer, testicular cancer, lung cancer, hepatocellular cancer, gastric cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, cancer of the urinary tract, cancer of reproductive organs thyroid cancer, renal cancer, carcinoma, melanoma, head and neck cancer, brain cancer (e.g., glioblastoma multiforme), prostate cancer, including but not limited to androgen-dependent prostate cancer and androgen-independent prostate cancer, and leukemia. Other cancer and cell proliferative disorders will be readily recognized in the art. The terms “tumor” and “cancer” are used interchangeably herein, e.g., both terms encompass solid and liquid, e.g., diffuse or circulating, tumors. As used herein, the term “cancer” or “tumor” includes premalignant, as well as malignant cancers and tumors. The term “cancer” is meant to include all types of cancerous growths or oncogenic processes, metastatic tissues or malignantly transformed cells, tissues, or organs, irrespective of histopathologic type or stage of invasiveness. Exemplary solid tumors include malignancies, e.g., adenocarcinomas, sarcomas, and carcinomas, of the various organ systems, such as those affecting breast, liver, lung, brain, lymphoid, gastrointestinal (e.g., colon), genitourinary tract (e.g., renal, urothelial cells), prostate and pharynx. Adenocarcinomas include cancers such as most colon cancers, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine and cancer of the esophagus. In one embodiment, the cancer is a melanoma, e.g., an advanced stage melanoma. Metastatic lesions of the aforementioned cancers can also be treated or prevented using the methods and compositions of the disclosure. Examples of other cancers that can be treated or prevented include pancreatic cancer, bone cancer, skin cancer, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the head or neck, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin Disease, non-Hodgkin lymphoma, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumors of childhood, lymphocytic lymphoma, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi&#39;s sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers including those induced by asbestos, and combinations of said cancers. Treatment of metastatic cancers, e.g., metastatic cancers that express PD-L1 (Iwai et al. (2005) Int. Immunol. 17:133-144) can be effected using the antibody molecules described herein. Exemplary cancers whose growth can be inhibited include cancers typically responsive to immunotherapy. Additionally, recurrent or are refractory malignancies can be treated using the molecules described herein. 
     “Chemotherapeutic agents” are compounds that are known to be of use in chemotherapy for cancer. Non-limiting examples of chemotherapeutic agents can include alkylating agents such as thiotepa and CYTOXAN® cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially calicheamicin gamma1I and calicheamicin omegaI1 (see, e.g., Agnew, Chem. Intl. Ed. Engl., 33: 183-186 (1994)); dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antiobiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN® doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elformithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2′,2″-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g., TAXOL® paclitaxel (Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE® Cremophor-free, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, Ill.), and TAXOTERE® doxetaxel (Rhone-Poulenc Rorer, Antony, France); chloranbucil; GEMZAR® gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin, oxaliplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE; vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (Camptosar, CPT-11) (including the treatment regimen of irinotecan with 5-FU and leucovorin); topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; capecitabine; combretastatin; leucovorin (LV); oxaliplatin, including the oxaliplatin treatment regimen (FOLFOX); lapatinib (Tykerb); inhibitors of PKC-alpha, Raf, H-Ras, EGFR (e.g., erlotinib (Tarceva®)) and VEGF-A that reduce cell proliferation and pharmaceutically acceptable salts, acids or derivatives of any of the above or combinations thereof “Chimeric antigen receptors” (CARs) are artificial (non-naturally occurring) immune cell (e.g., T cell) receptors contemplated for use as a therapy for cancer, using a technique called adoptive cell transfer. CARs are also known as artificial T-cell receptors, chimeric T-cell receptors or chimeric immunoreceptors. The antigen-binding, signaling, and stimulatory functions of the complex have been manipulated by genetic recombination methods to a single polypeptide chain, generally referred to as a Chimeric Antigen Receptor (CAR). See, e.g., Eshhar, U.S. Pat. No. 7,741,465; Eshhar, U.S. Patent Application Publication No. 2012/0093842. CARs are constructed specifically to stimulate T cell activation and proliferation in response to a specific antigen to which the CAR binds. Generally, a CAR refers to a set of polypeptides, typically two in the simplest embodiments, which when expressed in an immune effector cell, provides the cell with specificity for a target cell, typically a cancer cell, and with intracellular signal generation. In some embodiments, a CAR comprises at least an extracellular antigen binding domain, a transmembrane domain and a cytoplasmic signaling domain (also referred to herein as “an intracellular signaling domain”) comprising a functional signaling domain derived from a stimulatory molecule and/or costimulatory molecule. In some aspects, the set of polypeptides are contiguous with each other. In one aspect, the stimulatory molecule is the zeta chain associated with the T cell receptor complex. In one aspect, the cytoplasmic signaling domain further comprises one or more functional signaling domains derived from at least one costimulatory molecule as defined below. In one embodiment, the costimulatory molecule is chosen from the costimulatory molecules described herein, e.g., 4-1BB (i.e., CD137), CD27 and/or CD28. In one embodiment, the CAR comprises an optional leader sequence at the amino-terminus (N-ter) of the CAR fusion protein. In one embodiment, the CAR further comprises a leader sequence at the N-terminus of the extracellular antigen binding domain, wherein the leader sequence is optionally cleaved from the antigen binding domain (e.g., a scFv) during cellular processing and localization of the CAR to the cellular membrane. In various embodiments, CARs are recombinant polypeptides comprising an antigen-specific domain (ASD), a hinge region (HR), a transmembrane domain (TMD), an optional co-stimulatory domain (CSD) and an intracellular signaling domain (ISD). The optional costimulatory domain is generally absent in the 1″ generation CAR constructs. The target antigen, antigen binding domain name and nucleic acid sequences of several exemplary 1″ generation CARs comprising the different antigen binding domains (e.g., vL and vH fragments, vHH, ligands and receptors etc.) described in this disclosure and coexpressing the accessory modules encoding NEMO-K277A and PAC are presented in SEQ ID NO: 1594-1899 (Tables 12). These CAR constructs carry a human CD8 signal peptide, a CD8 hinge and transmembrane region and human CD3 intracellular signaling domain. These constructs also carry a MYC linker between the antigen binding domain and the CD8 hinge region, which is optional. The nucleic acid sequences of several exemplary 0 generation CARs comprising the different antigen binding domains (e.g., vL and vH fragments, vHH, ligands and receptors etc.) described in this disclosure and coexpressing the accessory modules encoding vFLIP K13 and PAC are presented in SEQ ID NO: 1016-1317 (Table 13). The nucleic acid sequences of several exemplary 2nd generation CARs comprising the different antigen binding domains (e.g., vL and vH fragments, vHH, ligands and receptors etc.) described in this disclosure and incorporating the 41BB costimulatory domain are presented in SEQ ID NO: 1318-1593 (Table 13). These CAR constructs also carry a MYC linker between the antigen binding domain and the transmembrane domain and an accessory module encoding puromycin resistance gene (PAC) that is separated from the CAR cassette by a Furine-SGSG-T2A sequence. The accessory module encoding vFLIP-K13, NEMO-K277A and PAC are optional in the above described 1″ and 2 nd  generation CARs. Thus, CARs with the antigen binding domains (i.e., vL and vH fragments, vHH, ligands and receptors etc.) described in this disclosure can be constructed without vFLIP-K13, NEMO-K277A and/or PAC. As such, these accessory modules along with the upstream cleavage linker sequences (e.g., F2A, P2A, or T2A) can be deleted from the CARs represented by SEQ ID NO: 1016-1899. Alternatively, the accessory module encoding vFLIP-K13, NEMO-K277A and/or PAC can be replaced by accessory modules encoding other proteins, such as hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, or IKK1-5176E-5180E, and MyD88-L265P, FKBPx2-NEMO, NEMO-L600-FKBPx2, TCL-1A, MTCP-1, and CMV-141 etc. As used herein, the term “CAR” or “CARs” also encompasses newer approaches to conferring antigen specificity onto cells, such as Antibody-TCR chimeric molecules or Ab-TCR or Ab-TCR (WO 2017/070608 A1 incorporated herein by reference), TCR receptor fusion proteins or TFP (WO 2016/187349 A1 incorporated herein by reference), Synthetic Immune Receptors (SIRs) (see, WO 2018/102795 A1, incorporated herein by reference), Tri-functional T cell antigen coupler (Tri-TAC) (see, WO 2015/117229 A1, incorporated herein by reference). The nucleic acid sequences of several exemplary TFPs comprising the different antigen binding domains (e.g., vL and vH fragments, vHH, ligands and receptors etc.) described in this disclosure and based on CD3c, CD3δ, CD3γ and CD3ζ chains and co-expressing the optional accessory module NEMO-K277A are presented in SEQ ID NO:1900-2205, 2206-2511, 2512-2817, 2818-3123, respectively (Table 13). The order of the antigen binding domains contained in the construct of different CAR architectures and BiTE listed in Table 13 is the same as the order of the constructs on the zCAR-K277A architecture presented in Table 12. Thus, the amino acid and nucleic acid SEQ ID NO of a CAR belonging to a given architecture (e.g., zCAR-K13) and containing a specific antigen binding domain can be determined by examination of Tables 12 and Table 13. Thus, Table 12 shows that a CAR on the zCAR-NEMO-K277A architecture and containing the huFMC63-11-(vL-vH) antigen binding domain is the 2nd construct in the Table 12 and is represented by nucleic acid and amino acid SEQ ID NOs: 1595 and 5508, respectively. The nucleic acid and amino acid SEQ ID Nos of a corresponding CAR on the zCAR-K13 architecture can be determine by examination of Table 13 which shows that the 2nd construct on this architecture has the nucleic acid and amino acid SEQ ID NOs: 1017 and 4930, respectively. A similar approach can be used to determine the nucleic acid and amino acid SEQ ID Nos of other CAR constructs belonging to different architectures and BiTEs. Table 10 provides the nucleic acid and amino acid SEQ ID Nos of several exemplary CARs belonging to different backbones and targeting HIV-1 Envelop Glycoprotein based on HIV1-N49P6 vL and vH antigen binding domains. Table 11 provides the nucleic acid and amino acid SEQ ID Nos of several exemplary CARs belonging to the backbones shown in Table 10 but containing different antigen binding domains. Thus, the nucleic acid and amino acid SEQ ID Nos of a CAR on a particular backbone containing the antigen binding domain shown in Table 11 can be determined by first determining its rank order in the Table 10. Thus, since the 1st generation CAR containing the vFLIP-K13 backbone is the third CAR on the list in Table 10, the nucleic acid SEQ ID NO of a 1st generation CAR co-expessing vFLIP-K13 and containing the HIV1-N49P7 antigen binding domain can be easily determined from Table 11 to be the SEQ ID NO: 8740 (i.e., the 3r d  construct in the series starting at 8738). Using a similar approach, the amino acid SEQ ID NO of this CAR construct is determined to be SEQ ID NO: 11438. As the CARs are modular in design, the nucleic acid and amino acid sequence of a CAR/BiTE containing different antigen binding domains or accessory modules can be easily determined by person with ordinary skill in the art by usinig the sequence of the different modules and exemplary CAR and BiTE constructs disclosed in this disclosure. Typically, “CAR-T cells” are used, which refer to T-cells that have been engineered to express a chimeric antigen receptor. Thus, T lymphocytes bearing such CARs are generally referred to as CAR-T lymphocytes. CARs can be also expressed in cells other than T cells, such as hematopoietic stem cells, induced pluripotent stem cells (iPSC), NK cells and macrophage. 
     “Codon optimization” or “controlling for species codon bias” refers to the preferred codon usage of a particular host cell. As will be understood by those of skill in the art, it can be advantageous to modify a coding sequence to enhance its expression in a particular host. The genetic code is redundant with 64 possible codons, but most organisms typically use a subset of these codons. The codons that are utilized most often in a species are called optimal codons, and those not utilized very often are classified as rare or low-usage codons. 
     Optimized coding sequences containing codons preferred by a particular prokaryotic or eukaryotic host (see also, Murray et al. (1989) Nucl. Acids Res. 17:477-508) can be prepared, for example, to increase the rate of translation or to produce recombinant RNA transcripts having desirable properties, such as a longer half-life, as compared with transcripts produced from a non-optimized sequence. Translation stop codons can also be modified to reflect host preference. Those of skill in the art will recognize that, due to the degenerate nature of the genetic code, a variety of DNA compounds differing in their nucleotide sequences can be used to encode a given polypeptide of the disclosure. 
     As used herein, “co-express” refers to expression of two or more polynucleotides or genes. Genes may be nucleic acids encoding, for example, a single protein or a chimeric protein as a single polypeptide chain. A CAR or a TCR described herein may be encoded by a single polynucleotide chain and expressed as single polypeptide chain, which is subsequently cleaved into different polypeptides, each representing a distinct functional unit. In some embodiments, where the CAR or a TCR consists of two or more functional polypeptide units, the different functional units are coexpressed using one or more polynucleotide chains. In one embodiment, costimulation is provided by an accessory module that is co-expressed with the CAR or a TCR but is not an integral part of the CAR or TCR polypeptide. Such an accessory module that provides costimulation to a CAR- or TCR-expressing cell or any cell but is not an integral part of the CAR or the TCR polypeptide is termed a CAR independent costimulatory module or CICM. In another embodiment, the different polynucleotide chains are linked by nucleic acid sequences that encode for cleavable linkers (e.g. T2A, F2A, P2A, E2A etc.) (Table 6D). In another embodiment, a Ser-Gly-Ser-Gly (SGSG) motif (SEQ ID NO: 4844) is also added upstream of the cleavable linker sequences to enhance the efficiency of cleavage. The polynucleotides encoding the different units of a CAR or a TCR may be linked by IRES (Internal Ribosomal Entry Site) sequences. Alternately, the different functional units of a CAR or TCR are encoded by two different polynucleotides that are not linked via a linker but are instead encoded by, for example, two different vectors. The nucleic acid and amino acid sequences of exemplary cleavable linkers and Furine cleavage sites are provided in Table 6D. 
     A “conservative substitution” or “conservative sequence modifications” refers to amino acid modifications that do not significantly affect or alter the binding characteristics or function of the encoded protein. For example, “conservative sequence modifications” refers to amino acid modifications that do not significantly affect or alter the binding characteristics or function of a CAR contruct of the disclosure (e.g., a conservative change in the constant chain, antibody, antibody fragment, or non-immunoglobulin binding domains). Such conservative modifications include amino acid substitutions, additions and deletions. Modifications can be introduced by standard techniques known in the art, such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions are ones in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, one or more amino acid residues within a CAR of the disclosure can be replaced with other amino acid residues from the same side chain family and the altered CAR can be tested using the binding and/or functional assays described herein. 
     The term “constant region of T cell receptor-alpha” or “constant chain of T cell receptor-alpha” or “TCRα” or “Ca” is defined as the protein provided as SEQ ID NO: 15041 or the equivalent residues (i.e., a homolog) from a non-human species, e.g., mouse, rodent, monkey, ape and the like. The disclosure also provides certain mutations to TCRα polypeptides which can be used in the construction of SIRs and Ab-TCR (Tables 3 and 6D). For example, sites of mutation in Cα that demonstrate increased expression and decreased mispairing are located at positions 91, 92, 93, and 94 of SEQ ID NO 15041. A TCR polypeptide with a Thr 48 Cys (T48C) mutation in Cα and a Ser-57-Cys (S57C) mutation in C1β1 or C1β2 chain (described more fully elsewhere herein) results in an additional disulfide bond between the two TCR constant chains (α and β). This, in turn, results in reduced mispairing with endogenous TCR chains in an immune cell and enhanced functionality. Similarly, a CAR with a Ser 61 Arg (S61R) mutation in Cα (SEQ ID NO:15048) and an Arg 79 Gly (R79G) mutation in C1β1 or C1β2 chain (described more fully elsewhere herein) results in reduced mispairing with the endogenous TCR chains and enhanced functionality due to a “knob and hole” design for pairing. The disclosure provides Cα polypeptides having one or more or all of the mutations according to Table 3 below which can be used in the construction of SIRs and Ab-TCR. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Mutations according to the disclosure in 
               
               
                 the human constant TCR-alpha region (Cα) 
               
            
           
           
               
               
               
               
            
               
                 Position 
                 Amino acid in 
                   
                   
               
               
                 (SEQ ID NO: 15041) 
                 wild-type 
                 Mutation 
                 TYPE 
               
               
                   
               
               
                 10 
                 Y 
                 C 
                 disulfide bond 
               
               
                 15 
                 S 
                 C 
                 disulfide bond 
               
               
                 45 
                 T 
                 C 
                 disulfide bond 
               
               
                 48 
                 T 
                 C 
                 disulfide bond 
               
               
                 61 
                 S 
                 R 
                 Knob into Hole 
               
               
                 91 
                 P 
                 S 
                 Murinization 
               
               
                 92 
                 E 
                 D 
                 Murinization 
               
               
                 93 
                 S 
                 V 
                 Murinization 
               
               
                 94 
                 S 
                 P 
                 Murinization 
               
               
                   
               
            
           
         
       
     
     The human genome encodes for two highly homologous TCR beta constant chains; TCR betal (TCRβ1 or TCRb1 or c1β1) and TCR beta 2 (TCRβ2 or TCRb2 or cβ2). The CARs of the disclosure can comprise either of these two chains. Similarly, either TCR betal or TCR beta2 chains of other mammalian species can be used in the methods of the disclosure. 
     The term “constant chain of T cell receptor-beta 1” or “constant region of T cell receptor-beta 1” (TCR-betal or TCRβ1 or TCRb1 or hTCR-betal or C1β1) is defined as a protein provided as SEQ ID NO: 15051 or the equivalent residues (i.e., a homolog) from a non-human species, e.g., mouse, rodent, monkey, ape and the like. 
     The term “constant chain of T cell receptor-beta 2” or “constant region of T cell receptor-beta 2” (TCR-beta2 or TCRβ2 or TCRb2 or C1β2) is defined as the protein provided as SEQ ID NO: 15052 or the equivalent residues (i.e., a homolog) from a non-human species, e.g., mouse, rodent, monkey, ape and the like. 
     The term “constant chain of T cell receptor-beta” or “constant region of T cell receptor-beta” (TCR-beta or TCRβ or TCRb or Cβ)” is defined as the protein provided as SEQ ID NO: 15051-15053 or the equivalent residues (i.e., a homolog) from a non-human species, e.g., mouse, rodent, monkey, ape and the like. 
     The protein sequences for both Cβ2 (SEQ ID NO: 15052) and Cβ1 (SEQ ID NO: 15051) are known (Table 6D). Differences between the sequences of Cβ2 and β1 are easily identified by alignment of the sequences using typical and ordinary skill in the art. The disclosure also provides certain mutations to TCRβ&#39;s that can be used in the construction of SIRs and Ab-TCRs. For example, sites of mutation in CDs that demonstrate increased expression and decreased mispairing with the endogenous TCRα chains are provided herein. These mutation sites in Cβ1 and Cβ2 are located at positions 18, 22, 57, 79 133, 136, and 139 of SEQ ID NOs: 15051 and 15052 and are summarized in the Tables 4 and 5 below. The mutation sites in Cβ1 and Cβ2 are identical in their positions. The only difference between the two sequences is that a mutation at position 136. At this position, a glutamic acid (E) is present in Cβ2, whereas a valine is present in Cβ1. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Mutations according to the disclosure in 
               
               
                 the human constant TCR-beta region1 (Cβ1) 
               
            
           
           
               
               
               
               
            
               
                 Position 
                 Amino acid in 
                   
                   
               
               
                 (SEQ ID NO: 15051) 
                 wild-type 
                 Mutation 
                 TYPE 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 15 
                 E 
                 C 
                 disulfide bond 
               
               
                 17 
                 S 
                 C 
                 disulfide bond 
               
               
                 18 
                 E 
                 K or R 
                 Murinization 
               
               
                 22 
                 S 
                 A 
                 Murinization 
               
               
                 57 
                 S 
                 C 
                 disulfide bond 
               
               
                 59 
                 D 
                 C 
                 disulfide bond 
               
               
                 77 
                 S 
                 C 
                 disulfide bond 
               
               
                 79 
                 R 
                 G 
                 Knob into Hole 
               
               
                 133 
                 F 
                 I 
                 Murinization 
               
               
                 136 
                 V 
                 A 
                 Murinization 
               
               
                 139 
                 Q 
                 H 
                 Murinization 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Mutations according to the disclosure in 
               
               
                 the human constant TCR-beta region2 (Cβ2) 
               
            
           
           
               
               
               
               
            
               
                 Position 
                 Amino acid in 
                   
                   
               
               
                 (SEQ ID NO: 15052) 
                 wild-type 
                 Mutation 
                 TYPE 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 15 
                 E 
                 C 
                 disulfide bond 
               
               
                 17 
                 S 
                 C 
                 disulfide bond 
               
               
                 18 
                 E 
                 K or R 
                 Murinization 
               
               
                 22 
                 S 
                 A 
                 Murinization 
               
               
                 57 
                 S 
                 C 
                 disulfide bond 
               
               
                 59 
                 D 
                 C 
                 disulfide bond 
               
               
                 77 
                 S 
                 C 
                 disulfide bond 
               
               
                 79 
                 R 
                 G 
                 Knob into Hole 
               
               
                 133 
                 F 
                 I 
                 Murinization 
               
               
                 136 
                 E 
                 A 
                 Murinization 
               
               
                 139 
                 Q 
                 H 
                 Murinization 
               
               
                   
               
            
           
         
       
     
     The term “constant chain of TCR-gamma” or “constant region of TCR-gamma” (TCR-gamma or TCRγ or TCRg or TCR-gammal or TCRy1 or TCRg1 or Cy) is defined as the protein provided as SEQ ID NO: 15068 or the equivalent residues (i.e., a homolog) from a non-human species, e.g., mouse, rodent, monkey, ape and the like. 
     The term “constant chain of TCR-delta” or “constant region of TCR-delta” (TCR-delta or TCRδ or TCRd or Cδ) is defined as the proteins provided as SEQ ID NO: 15069 or the equivalent residues (i.e., a homolog) from a non-human species, e.g., mouse, rodent, monkey, ape and the like. 
     It will be recognized that proteins can have identity or homology to one another and retain similar or identical functions. The disclosure includes TCR constant regions that have 85%, 90%, 95%, 97%, 98%, 98.5%, 99% or 99.9% identity to any of the sequences described herein while retaining the biological activity. 
     Accordingly, the disclosure provides a T-cell receptor constant chain having a sequence selected from the group consisting of: (a) an amino acid sequence that is at least 98% identical to SEQ ID NO:15041 and which can have one or more mutations at positions 61, 91, 92, 93, and/or 94; (b) an amino acid sequence that is at least 98% identical to SEQ ID NO:15051 and can have one or more mutations at positions 18, 22, 57, 79, 133, 136 and/or 139; (c) an amino acid sequence that is at least 98% identical to SEQ ID NO:15052 and can have one or more mutations at position 18, 22, 57, 79, 133, 136 and/or 139; (d) an amino acid sequence that is at least 98% identical to SEQ ID NO:15068; and (e) an amino acid sequence that is at least 98% identical to SEQ ID NO:15069. The T-cell receptor constant chains of any of (a)-(e) retain at least one biological activity of the wild-type T-cell receptor constant chain to which it has identity or homology. 
     The term “constitutively active” refers to a molecule, e.g., a protein, that has signaling activity without the need of a stimulus. Exemplary constitutive active proteins are NEMO-K277A and vFLIP K13 as they can activate NF-κB signaling when expressed in a suitable cell without the need of an additional stimulus. 
     The term a “costimulatory molecule” or a “costimulatory receptor” refers to a cognate binding partner on a T cell that specifically binds with a costimulatory ligand, thereby mediating a costimulatory response by the T cell, such as, but not limited to, proliferation. Costimulatory extracellular molecules are cell surface molecules other than antigen receptors or their ligands that contribute to an efficient immune response. Costimulatory molecules include, but are not limited to an MHC class I molecule, BTLA and a Toll ligand receptor, as well as OX40, Dapl0, CD27, CD28, CD2, CDS, CD8, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), Lck, TNFR-I, TNFR-II, Fas, CD30, CD40 and 4-1BB (CD137). Further examples of such costimulatory molecules include CD8, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD160, CD19, CD4, CD8alpha, CD8beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CDlld, ITGAE, CD103, ITGAL, CDlla, LFA-1, ITGAM, CD11b, ITGAX, CDllc, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, NKG2D, NKG2C, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRT AM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IP0-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, CD19a, and a ligand that specifically binds with CD83. A co-stimulatory receptor may be expressed on cells other T cells, such as NK cells or macrophages. 
     A “costimulatory intracellular signaling domain” or “costimulatory domain” (CSD) can be the intracellular portion of a costimulatory receptor. A costimulatory molecule can be represented in the following protein families: TNF receptor proteins, Immunoglobulin-like proteins, cytokine receptors, integrins, signaling lymphocytic activation molecules (SLAM proteins), and activating NK cell receptors. Examples of such molecules include CD27, CD28, 4-1BB (CD137), OX40, GITR, CD30, CD40, ICOS, BAFFR, HVEM, ICAM-1, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD8, CD7, CD287, LIGHT, NKG2C, NKG2D, SLAMF7, NKp80, NKp30, NKp44, NKp46, CD160, B7-H3, and a ligand that specifically binds with CD83, and the like. The intracellular signaling domain can comprise the entire intracellular portion, or the entire native intracellular signaling domain, of the molecule from which it is derived, or a functional fragment or derivative thereof. The CARs of the disclosure may comprise one or more co-stimulatory domains. 
     The term “cTCR” refers to a wild-type TCR nucleic acid coding sequence and the corresponding wild-type TCR protein linked to an antigen binding domain. cTCRs are used in some embodiments and reference controls. For example, a cTCR having a CD19 binding domain and a CD19-CAR (comprising a mutant TCR chain and CD19 binding domain) will have different expression and/or difference binding affinities to the target antigen. 
     The term “cytosolic” or “cytoplasmic” refers to an agent, e.g., a protein, that is situated in the cytoplasm of a cell in its mature form. A cytosolic protein can translocate into the nucleus but is not a transmembrane protein and is not secreted outside the cell. An exemplary cytosolic protein is vFLIP K13. 
     The term “degenerative disorders” refers to a disease that is the result of a continuous process based on degenerative cell changes, affecting tissues or organs, which will increasingly deteriorate over time, whether due to normal bodily wear or lifestyle choices such as exercise or eating habits. Exemplary degenerative diseases include Alzheimer&#39;s disease, Charcot—Marie—Tooth disease, Creutzfeldt—Jakob disease, Friedreich&#39;s ataxia, Diabetes mellitus (type II), and Atherosclerosis. 
     “Derived from” as that term is used herein, indicates a relationship between a first and a second molecule. It generally refers to structural similarity between the first molecule and a second molecule and does not connotate or include a process or source limitation on a first molecule that is derived from a second molecule. For example, in the case of an antigen binding domain that is derived from an antibody molecule, the antigen binding domain retains sufficient antibody structure such that is has the required function, namely, the ability to bind to an antigen. It does not connotate or include a limitation to a particular process of producing the antibody, e.g., it does not mean that, to provide the antigen binding domain, one must start with an antibody sequence and delete unwanted sequence, or impose mutations, to arrive at the antigen binding domain. 
     “Dimerization molecule,” as that term is used herein refers to a molecule that promotes the association of a first switch domain with a second switch domain. In embodiments, the dimerization molecule does not naturally occur in the subject, or does not occur in concentrations that would result in significant dimerization. In embodiments, the dimerization molecule is a small molecule, e.g., rapamycin or a rapalogue, e.g, RAD001, Rimiducid or AP20187. Rimiducid (AP1903) is a lipid-permeable tacrolimus analogue with homodimerizing activity. Rimiducid homodimerizes an analogue of human protein FKBP12 (Fv) which contains a single acid substitution (Phe36Val). Rimiducid is used to homodimerize the Fv-containing drug-binding domains of non-naturally occurring immune receptor resulting in downstream signaling activation during cell therapy. Rimiducid can be at about 0.01-1 mg/kg and has an EC50 in cell culture of about 0.1nM. AP20187 can be administered from about 2-10 mg/kg/day in single or multi-doses. 
     The phrase “disease associated with expression of a target antigen” or “disease associated antigen as described herein” includes, but is not limited to, a disease associated with expression of a target antigen as described herein or condition associated with cells which express a target antigen as described herein including, e.g., proliferative diseases such as a cancer or malignancy or a precancerous condition such as a myelodysplasia, a myelodysplastic syndrome or a pre leukemia; or a noncancer related indication associated with cells which express a target antigen as described herein. In one aspect, a cancer associated with expression of a tumor antigen as described herein is a hematological cancer. In one aspect, a cancer associated with expression of a tumor antigen as described herein is a solid cancer. Further diseases associated with expression of a tumor antigen described herein include, but are not limited to, atypical and/or non-classical cancers, malignancies, precancerous conditions or proliferative diseases associated with expression of a tumor antigen as described herein. Non-cancer related indications associated with expression of a target antigen as described herein include, but are not limited to, e.g., autoimmune disease, (e.g., lupus), inflammatory disorders (allergy and asthma) and transplantation. In some embodiments, the target antigen-expressing cells express, or at any time expressed, mRNA encoding the target antigen. In another embodiment, the target antigen -expressing cells produce the target antigen protein (e.g., wild-type or mutant), and the target antigen protein may be present at normal levels or reduced levels. In another embodiment, the target antigen -expressing cells produced detectable levels of a target antigen protein at one point, and subsequently produced substantially no detectable target antigen protein. 
     “Disease targeted by genetically modified cells” as used herein encompasses the targeting of any cell involved in any manner in any disease by the genetically modified cells of the invention, irrespective of whether the genetically modified cells target diseased cells or healthy cells to effectuate a therapeutically beneficial result. The genetically modified cells include but are not limited to genetically modified T-cells, NK cells, hematopoietic stem cells, pluripotent embryonic stem cells or embryonic stem cells. The genetically modified cells express the conventional CARs and novel backbones containing conventional CARs with accessory modules of the invention, which CARs may target any of the antigens expressed on the surface of target cells. Examples of antigens which may be targeted include but are not limited to antigens expressed on B-cells; antigens expressed on carcinomas, sarcomas, lymphomas, leukemia, germ cell tumors, and blastomas; antigens expressed on various immune cells; and antigens expressed on cells associated with various hematologic diseases, autoimmune diseases, and/or inflammatory diseases. Other antigens that may be targeted will be apparent to those of skill in the art and may be targeted by the CARs of the invention in connection with alternate embodiments thereof. 
     The term “Dissociation constant (Kd)” is defined as the equilibrium constant of the dissociation of a receptor—ligand interaction. 
     As used herein a “diverse set of non-naturally occurring immune receptors” or “diverse set of SIRs” or “diverse set of CARs” refers to a plurality of non-naturally occurring immune receptors having the same binding domain linked to a diverse set of T cell receptor constant chains or “backbones” wherein each construct comprising a binding domain and a different T cell constant chain or backbone provide a diverse range of binding to a target antigen and/or varied expression levels. For example, depending upon the mutation composition of the constant domain (e.g., mutant TCRa+TCRb), the binding affinity of the binding domain to its target varies. In some embodiments, a SIR of the disclosure (single strand or heterodimer) comprises a binding affinity that is greater than a wild-type TCR (e.g., cTCR) with the same binding domain. In one embodiment a SIR has a higher expression level than a cTCR by at least 1.25 fold to about 10,000 fold higher (and any number in between), wherein the SIR and cTCR differ only in the mutation in the TCR domain. In another embodiment, a SIR has a binding affinity for a target that is at least 1.5 fold higher to about 10,000 fold higher than a cTCR having a binding domain to the same antigen. In yet another embodiment, the SIR has a higher binding affinity than a cTCR to the same antgen, but less than a chimeric antigen receptor (CAR) having the same binding domain. In some embodiments, the binding of a SIR expressing effector cell to the target antigen is at least 1.25-fold more than the binding of a corresponding cTCR-expressing effector cell but less than 100,000 fold more than the corresponding cTCR. In some embodiment, the antigen binding domain has a disassociation constant (KD, reflecting its binding affinitiy) from between about 10 −4  M to 10 −8 M. In some embodiments, the antigen bidning domain binds to one or more of the antigents recited above. In some embodiment, the antigen binding domain has a K D  of between about 10 −4 M to 10 −8 M, e.g., betweeon about 10 −5 M to 10 −7 M, e.g., between about10 −5 M to 10 −6  M, for the target antigen. In one embodiment, the binding affinity of the antigen binding domain is at least five-fold, 10-fold, 20-fold, 30-fold, 50-fold, 100-fold or 1,000-fold less than a reference antibody. In one embodiment, the encoded antigen binding domain has a binding affinity at least 5-fold less than a reference antibody. In some embodiments, the reference antibody is an antibody from which the antigen binding domain is derived. For example, the disclosure contemplates a diverse population of SIRs against a particular antigen target that can be designed and screened based upon the nucleic acid sequence codon optimization and/or the mutation in the TCR chain to promote pairing or expression and/or the use of a linker between the binding domain and the TCR domain. 
     As used herein, an “epitope” is defined to be the portion of an antigen capable of eliciting an immune response, or the portion of an antigen that binds to an antibody or antibody fragment. Epitopes can be a protein sequence or subsequence. 
     The term “expression vector” refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, including cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adena-associated viruses) that incorporate the recombinant polynucleotide. 
     The term “functional portion” when used in reference to a CAR refers to any part or fragment of the CAR, which part or fragment retains the biological activity of the CAR of which it is a part (the parent CAR). Functional portions encompass, for example, those parts of a CAR that retain the ability to recognize target cells, or detect, treat, or prevent a disease, to a similar extent, the same extent, or to a higher extent, as the parent CAR. In reference to the parent CAR, the functional portion can comprise, for instance, about 10%, 25%, 30%, 50%, 68%, 80%, 90%, 95%, or more, of the parent CAR. 
     “Genetically modified cells”, “redirected cells”, “genetically engineered cells” or “modified cells” as used herein refer to cells that express a CAR of the disclosure. In some embodiments, the genetically modified cells comprise vectors that encode a CAR. In some embodiments, the genetically modified cells comprise vectors that encode a CAR and one or more accessory molecules in the same vector. In some embodiments, the genetically modified cells comprise a first vector that encodes a CAR and a second vector that encodes the accessory molecule. In some embodiments, the genetically modified cells comprise a first vector that encodes a CAR and a second vector that encodes more than one accessory molecule. In some embodiments, the genetically modified cells comprise a first vector that encodes a CAR and a second vector that encodes the first accessory molecule and a third vector that encodes a second accessory molecule. 
     “Hinge region” (HR) as used herein refers to the hydrophilic region which is between the antigen binding domain and the transmembrane domain. The hinge regions include but are not limited to Fc fragments of antibodies or fragments or derivatives thereof, hinge regions of antibodies or fragments or derivatives thereof, CH2 regions of antibodies, CH3 regions of antibodies, artificial spacer sequences or combinations thereof. Examples of hinge regions include but are not limited to CD8a hinge, and artificial spacers made of polypeptides which may be as small as, for example, Gly3 or CH1 and CH3 domains of IgGs (such as human IgG4). In some embodiments, the hinge region is any one or more of (i) a hinge, CH2 and CH3 regions of IgG4, (ii) a hinge region of IgG4, (iii) a hinge and CH2 of IgG4, (iv) a hinge region of CD8a, (v) a hinge, CH2 and CH3 regions of IgG1, (vi) a hinge region of IgG1 or (vi) a hinge and CH2 region of IgG1. Other hinge regions will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the disclosure. 
     The term “immune disorder” refers to a disease characterized by dysfunction of immune system. An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. 
     “Immune cell” as used herein refers to the cells of the mammalian immune system including but not limited to antigen presenting cells, B-cells, basophils, cytotoxic T-cells, dendritic cells, eosinophils, granulocytes, helper T-cells, leukocytes, lymphocytes, macrophages, mast cells, memory cells, monocytes, natural killer cells, neutrophils, phagocytes, plasma cells and T-cells. 
     “Immune effector cell,” as that term is used herein, refers to a cell that is involved in an immune response, e.g., in the promotion of an immune effector response. Examples of immune effector cells include T cells, e.g., alpha/beta T cells and gamma/delta T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells, and myeloic-derived phagocytes. 
     “Immune effector function” or “immune effector response,” “effector function” refers to the specialized function of a differentiated cell. Effector function of a T-cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines. For example, an immune effector function or response refers a property of a T or NK cell that promotes killing or the inhibition of growth or proliferation, of a target cell. In the case of a T cell, primary stimulation and co-stimulation are examples of immune effector function or response. In case of antigen presenting cells (e.g., dendritic cells) antigen presentation and cytokine secretion are examples of effector functions. 
     “Immune response” as used herein refers to immunities including but not limited to innate immunity, humoral immunity, cellular immunity, immunity, inflammatory response, acquired (adaptive) immunity, autoimmunity and/or overactive immunity. 
     An “intracellular signaling domain,” (ISD) or “cytoplasmic domain” as the term is used herein, refers to an intracellular signaling portion of a molecule. The intracellular signaling domain generates a signal that promotes an immune effector function of the cell. Examples of immune effector function include cytolytic activity and helper activity, including the secretion of cytokines. Examples of domains that transduce the effector function signal include but are not limited to the z chain of the T-cell receptor complex or any of its homologs (e.g., h chain, FceRlg and b chains, MB1 (Iga) chain, B29 (Igb) chain, etc.), human CD3 zeta chain, CD3 polypeptides (D, d and e), syk family tyrosine kinases (Syk, ZAP 70, etc.), src family tyrosine kinases (Lck, Fyn, Lyn, etc.) and other molecules involved in T-cell transduction, such as CD2, CD5 and CD28. Other intracellular signaling domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the disclosure. 
     In another embodiment, the intracellular signaling domain can comprise a primary intracellular signaling domain. Exemplary primary intracellular signaling domains include those derived from the molecules responsible for primary stimulation, or antigen dependent simulation. In another embodiment, the intracellular signaling domain can comprise a costimulatory intracellular domain. Exemplary costimulatory intracellular signaling domains include those derived from molecules responsible for costimulatory signals, or antigen independent stimulation. For example, a primary intracellular signaling domain can comprise a cytoplasmic sequence of CD3z, and a costimulatory intracellular signaling domain can comprise cytoplasmic sequence from co-receptor or costimulatory molecule, such as CD28 or 41BB. 
     A primary intracellular signaling domain can comprise a signaling motif which is known as an immunoreceptor tyrosine-based activation motif or ITAM. Examples of ITAM containing primary cytoplasmic signaling sequences include, but are not limited to, those derived from CD3 zeta, common FeR gamma (FCER1G), Fe gamma RIIa, FeR beta (Fe Epsilon Rib), CD3 gamma, CD3 delta, CD3 epsilon, CD79a, CD79b, DAP1O, and DAP12. 
     The term “isolated” as used herein refers to molecules or biologicals or cellular materials being substantially free from other materials. In one aspect, the term “isolated” refers to nucleic acid, such as DNA or RNA, or protein or polypeptide (e.g., an antibody or derivative thereof), or cell or cellular organelle, or tissue or organ, separated from other DNAs or RNAs, or proteins or polypeptides, or cells or cellular organelles, or tissues or organs, respectively, that are present in the natural source. The term “isolated” also refers to a nucleic acid or peptide that is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Moreover, an “isolated nucleic acid” is meant to include nucleic acid fragments which are not naturally occurring as fragments and would not be found in the natural state. The term “isolated” is also used herein to refer to polypeptides which are isolated from other cellular proteins and is meant to encompass both purified and recombinant polypeptides. The term “isolated” is also used herein to refer to cells or tissues that are isolated from other cells or tissues and is meant to encompass both, cultured and engineered cells or tissues. 
     As used herein, the term “linker” (also “linker domain” or “linker region”) referes to an oligo or a polypeptide (or an oligo encoding the polypeptide) that joins together two or more domains or regions of a CAR polynucleotide or polypeptide, respectively, disclosed herein. The linker can be anywhere from 1 to 500 amino acids in length or 3 to 1500 nucleotide in length. In some embodiments the “linker” is cleavable or non-cleavable. Unless specified otherwise, the term “linker” used herein means a non-cleavable linker. Said non-cleavable linkers may be composed of flexible residues which allow freedom of motion of adjacent protein doamins relative to one another. Non-limiting examples of such residues include glycine and serine. In some embodiments, linkers include non-flexible residues. Examples of cleavable linkers include 2A linkers (for example T2A), 2A-like linkers or functional equivalents thereof and combinations thereof. In some embodiments, the linkers include the picornaviral 2A-like linker, CHYSEL sequences of porcine teschovirus (P2A), Thosea asigna virus (T2A) or combinations, variants and functional equivalents thereof. In some embodiments, the linker sequences may comprise a motif that results in cleavage between the 2A glycine and the 2B proline (see, e.g., T2A sequence, SEQ ID NO: 4839 and 4840, C-terminal Gly-Pro). The nucleic sequences of several exemplary cleavable linkers are provided in SEQ ID NO: 925 to SEQ ID NO: 930 and amino acid sequences of several exemplary linkers are provided in SEQ ID NO: 4838 to SEQ ID NO: 4843. Other clevable linkers that may be used herein are readily appreciated by those of skill in the art. 
     In an embodiment, a Ser-Gly-Ser-Gly (SGSG) motif (SEQ ID NOs: 931-32) is also added upstream of the cleavable linker sequences to enhance the efficiency of cleavage. A potential drawback of the cleavable linkers is the possibility that the small 2A tag left at the end of the N-terminal protein may affect protein function or contribute to the antigenicity of the proteins. To overcome this limitation, in some embodiments, a furine cleavage site (RAKR) (SEQ ID NO: 933-935) is added upstream of the SGSG motifs to facilitate cleavage of the residual 2A peptide following translation. 
     The term “flexible polypeptide linker” as used herein refers to a peptide linker that consists of amino acids such as glycine and/or serine residues used alone or in combination, to link polypeptide chains together (e.g., variable heavy and variable light chain regions together). In one embodiment, the flexible polypeptide linker is a Gly/Ser linker and comprises the amino acid sequence (Gly-Gly-Gly-Ser) n , (SEQ ID NO:4191-4192) where n is a positive integer equal to or greater than 1. For example, n=1, n=2, n=3. n=4, n=5 and n=6, n=7, n=8, n=9 and n=10. In one embodiment, the flexible polypeptide linkers include, but are not limited to, (Gly4Ser)4 or (Gly4Ser)3 (SEQ ID NO:4193 or 4194). Also included within the scope of the disclosure are linkers described in W02012/138475, incorporated herein by reference). 
     The term “lentivirus” refers to a genus of the Retroviridae family. Lentiviruses are unique among the retroviruses in being able to infect non-dividing cells; they can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of a gene delivery vector. HIV, SIV, and FIV are all examples of lenti viruses. 
     The term “lentiviral vector” refers to a vector derived from at least a portion of a lentivirus genome, including especially a self-inactivating lentiviral vector as provided in Milone et al., Mol. Ther. 17(8): 1453-1464 (2009). Other examples of lentivirus vectors that may be used in the clinic, include but are not limited to, e.g., the LENTIVECTOR® gene delivery technology from Oxford BioMedica, the LENTIMAXTM vector system from Lentigen and the like. Nonclinical types of lentiviral vectors are also available and would be known to one skilled in the art. Other examples of lentivirus vectors are pLENTI-EF1α (SEQ ID NO: 3837), pLENTI-EF1a-DWPRE (SEQ ID NO: 3838), pCCLc-MNDU3-WPRE (SEQ ID NO: 7779) and pCCLc-MNDU3-Eco-Nhe-Sal-WPRE (SEQ ID NO: 7780). pLenti-EF1a-DWPRE was derived from the pLENTI-EF1a vector by deletion of WPRE sequence. An internal Sac II fragment was deleted from the EF 1 a promoter to generate EF 1 alpha (EF1a)-D-SACII-Promoter (SEQ ID NO: 3842). In an exemplary embodiment, the nucleic acid fragment encoding a CAR, CAR plus accessory module(s), or the accessory module(s) can be cloned between the Nhe I and Sal I sites present in the pLENTI-EF1a and the pCCLc-MNDU3-Eco-Nhe-Sal-WPRE vectors using methods known in the art. 
     “Mammal” as used herein refers to any member of the class Mammalia, including, without limitation, humans and nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be included within the scope of this term. 
     “Naked DNA” as used herein refers to DNA encoding a CAR cloned in a suitable expression vector in proper orientation for expression. Viral vectors which may be used include but are not limited SIN lentiviral vectors, retroviral vectors, foamy virus vectors, adeno-associated virus (AAV) vectors, hybrid vectors and/or plasmid transposons (for example sleeping beauty transposon system) or integrase based vector systems. Other vectors that may be used in connection with alternate embodiments of the invention will be apparent to those of skill in the art. 
     “Native” or “Naturally occurring” or “endogenous” as used herein refers to a gene, protein, nucleic acid (e.g., DNA, RNA etc.) or fragment thereof that is native to a cell or is naturally expressed in a cell. Thus, a native or endogenous TCRα chain polypeptide of a T cell consists of a variable domain (Va) joined to a TCRα constant chain. The native or endogenous TCRα chain precursor polypeptide also consists of an amino-terminal signal peptide that is cleaved from the mature polypeptide. 
     NF-Kappa-B Essential Modulator (NEMO) refers to a scaffolding protein component of IκB kinase complex required for NF-κB activation. NF-κB is a transcription factor that controls inflammation, cell proliferation and apoptosis. 
     “NF-κB pathway” or “NF-κB signaling pathway” refers to a signal transducton pathway that results in the nuclear translocation of NF-κB subunits and transcriptional activation of NF-κB subunit responsive genes. NF-κB refers to family of transcription factors that are involved in the regulated expression of several genes involved in the inflammatory and immune response. Five known members of this family have been characterized to date and include c-Rel, NF-κB1 (p50 and its precursor p105), NF-κB2 (p52 and its precursor p105), p65(RelA) and RelB. Although many dimeric forms of NF-κB have been described, the classical NF-κB complex is a heterodimer of the p65/RelA and p50 subunits and is found in most cells in association with a family of inhibitory proteins, called IκBs, of which the most common is IκBa. In the classical NF-κB pathway, stimulation by a number of cytokines, such as TNFa and IL-1, results in the activation of a multi-subunit IκB kinase (IKK) complex, which contains two catalytic subunits, IKK1/IKKa and IKK2/IKKP, and a regulatory subunit, NEMO/IKKγ. The activated IKK complex leads to the inducible phosphorylation of IκB proteins and their subsequent degradation, thereby releasing NF-κB from their inhibitory influence. Once released, NF-κB is free to migrate to the nucleus and bind to the promoter of specific genes possessing its cognate binding site. The transcriptional activity of the NF-κB dimers in the nucleus is further modified by their phosphorylation. An an alternative (or noncanonical) pathway of NF-κB activation, that involves proteasome-mediated processing of p100/NF-κB2 into p52 subunit, has been described. 
     “NF-κB stimulatory molecule” or “NF-κB stimulator” or “NF-κB activator” refers to a subset of accessory molecules that promote the activity of the NF-κB signaling pathway or the activity/expression of the downstream target genes of the NF-κB signaling pathway. In some embodiments, a NF-κB activator is a non-naturally occurring NF-κB activating agent. An exemplary non-naturally occurring NF-κB activating agent is hNEMO-K277A. In one embodiment, the NF-κB stimulatory molecule or NF-κB stimulator is a selective NF-κB stimulator or a selective NF-κB activator. A “selective NF-κB activator” or a “selective NF-κB stimulator” as described herein, refers to an agent that activates the NF-κB signaling pathway selectively with no or minimal activation of the other signaling pathways. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of one or more of signaling pathways selected from the group of AKT, PI3K, JNK, p38 kinase, ERK, JAK/STAT and interferon signaling pathways. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of AKT signaling pathway. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of AKT signaling pathway. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of PI3K signaling pathway. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of ERK signaling pathway. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of JNK signaling pathway. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of p38 kinase signaling pathway. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of JAK/STAT signaling pathway. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of interferon signaling pathway. A number of methods to measure the activation of the NF-κB signaling pathways are known in the art, including but not limited to measurement of phosphorylated IκBa, phosphorylated p65/RelA, total IκBa, p65 nuclear translocation, upregulation of NF-κB responsive genes, electrophoretic mobility-shift assay (EMSA) and NF-κB-based reporter assay etc. These assays can be used in the methods of the disclosure either singly or in combinations to identify selective activators of NF-κB pathway. A number of methods to measure the activation of the signaling pathways (e.g., AKT, PI3K, JNK, p38 kinase, ERK, JAK/STAT and interferon signaling pathways) are known in the art, including but not limited to measurement of phosphorylation of the different kinases and downstream substrates belonging to the different pathways, nuclear translocation of downstream transcription factors, upregulation of the downstream responsive genes, electrophoretic mobility shift assay (EMSA) and luciferase based reporter assay etc. These assays can be used in the methods of the disclosure either singly or in combinations to select selective activators of NF-κB signaling pathway. A selective NF-κB stimulator specifically activates NF-κB compared to other accessory molecules such as 41BB. A NF-κB stimulatory molecule, including a selective NF-κB activator, has one or more of the following effects: (i) extend the life span of T cells, e.g., CAR-T cells or TCR-T cells, (ii) stimulate T cell proliferation, (iii) protect T cells, e.g., CAR-T cells, from apoptosis, (iv) delay senescence of T cells, e.g., CAR-T cells or TCR-T cells (v) delay exhaustion of T cells, e.g., CAR-T cells or TCR-T cells, (vi) delay terminal differentiation of T cells, (vii) promote production of cytokines, such as IL2, by T cells, (viii) promote in vivo expansion of T cells, including CAR-T cells and TCR-T cells, (ix) promote in vivo persistence of T cells, including CAR-T cells and TCR-T cells, (x) improve the in vivo activity (e.g., anti-tumor activity) of the T cells, including CAR-T and TCR-T cells. A NF-κB stimulatory molecule, including a selective NF-κB activator, may be expressed in cells other than T cells, such as antigen presenting cells, e.g., dendritc cells. A NF-κB stimulatory molecule, including a selective NF-κB activator, may be used to enhance the antigen presention, cytokine production and immune response generated by antigen presenting cells. An NF-κB stimulatory molecule, including a selective NF-κB activator, may be of viral or non-viral (e.g., human) origin. An NF-κB stimulatory molecule, including a selective NF-κB activator, may be expressed in a cell transiently or stably. An NF-κB stimulatory molecule, including a selective NF-κB activator, may be expressed in a cell in a constitutive or inducible manner. An NF-κB stimulatory molecule, including a selective NF-κB activator, may be expressed in a cell in fusion with a switch domain, e.g., tandem copies of a FKBP12v36 domain. Exemplary switch domain containing NF-κB stimulatory molecules are provided in SEQ ID NO: 973-977, 1006-1009, 7763-7767 and 7781-7782 (Table 7). An NF-κB stimulatory molecule, including a selective NF-κB activator, can be expressed from a vector containing a coding sequence for a CAR/TCR or may be present on a different vector. For example, in some embodiments, vectors comprising polynucleotides encoding CARs/TCRs further comprise polynucleotides encoding viral and cellular signaling proteins which are NF-κB stimulatory molecule or selective NF-κB activator that (i) extend the life span of T cells, e.g., CAR-T cells or TCR-T cells, (ii) stimulate T cell proliferation, (iii) protect T cells, e.g., CAR-T cells, from apoptosis, (iv) delay senescence of T cells, e.g., CAR-T cells or TCR-T cells (v) delay exhaustion of T cells, e.g., CAR-T cells or TCR-T cells, (vi) delay terminal differentiation of T cells, (vii) promote production of cytokines, such as IL2, by T cells, (viii) promote in vivo expansion of T cells, including CAR-T cells and TCR-T cells, (ix) promote in vivo persistence of T cells, including CAR-T cells and TCR-T cells, and/or (x) improve the in vivo activity (e.g., anti-tumor activity) of the T cells, including CAR-T and TCR-T cells. In some embodiments, the coding sequence for a NF-κB stimulatory molecule is linked to a CAR backbone coding sequence by an oligonucleotide encoding a cleavable linker. In exemplary embodiments, such NF-κB stimulatory molecules include but are not limited to vFLIP-K13 from Kaposi&#39;s sarcoma associated herpes virus, a codon optimized K13 (K13-opt), NEMO mutant ((e.g, hNEMO-K277A, hNEMO-K277L, hNEMO-K277A-deltaV249-K255, mNEMO-K270A etc), IKK2-S177E-S181E, IKK1-S176E-S180E, MyD88-L265P, TCL-1A, MTCP-1, IKKα, and IKKδ (Table 7). In one embodiment, vectors encoding CARs further encode vFLIP-K13. In another embodiment, vectors encoding CARs further encode hNEMO-K277A. In some embodiments, the NF-κB stimulatory molecule is encoded by a vector that is distinct from the vector encoding the CAR described herein. In some embodiments, effector cells comprising vectors encoding CARs also comprise vectors encoding NF-κB stimulatory molecule. In some embodiments, the NF-κB stimulatory molecules are encoded by modifying the genomic locus encoding the corresponding endogenous protein. For example, one or more copies of hNEMO gene can be modified by homologous recombination to mutate it to K277A mutant form. An exemplary targeting constructs that can be used to create K277A mutation in the endogenous human NEMO gene is presented by SEQ ID NO: 7771. An exemplary targeting constructs that can be used to create K277A-Delta-V249-K255 mutation in the endogenous human NEMO gene is presented by SEQ ID NO: 7772. These targeting constructs can be introduced into human T cells with a gene editing system targeting NEMO, e.g., CRISP/Cas9 or TALON, using techniques known in the art. Exemplary NEMO gRNA target sequences for Streptococcus Pyogenes Cas9 are provided in SEQ ID NO: 7759-7762. In one embodiment, the CAR and the NF-κB stimulatory molecule are encoded by a single polynucleotide. In another embodiment, the CAR is encoded by the first nucleic acid molecule and the NF-κB stimulatory molecule is encoded by a second nucleic acid molecule. In some embodiments, the NF-κB stimulatory molecule is encoded by more than one nucleic acid molecule, depending on the number of NF-κB stimulatory molecules. In certain portions of the disclosure the abbreviation “CAR/NFKB” is used to indicate, for example, a cell that expresses both a CAR of the disclosure and an NF-κB stimulatory molecule (e.g., a NF-κB specific stimulatory molecule). For example, the term “CAR/NFκB-expressing T cell” refers to a CAR-T cells having any number of possible different antigen binding domains that also expresses, for example, an NF-κB specific stimulatory molecule selected from the group consisting of vFLIP-K13 from Kaposi&#39;s sarcoma associated herpes virus, a codon optimized K13 (K13-opt), hNEMO-K277A, hNEMO-K277A-deltaV249-K555, mNEMO-K270A, IKK2-S177E-S181E, IKK1-S176E-S180E, MyD88-L265P, TCL-1A, MTCP-1, IKK1/IKKa, and IKK2/IKKβ, or any combination thereof. The NF-κB stimulatory molecule may be directly linked to the cytoplasmic domain of the CAR or may be independently expressed in the cell. The NF-κB stimulatory molecule may be a molecule that blocks the expression and or activity of an inhibitor of NF-κB signaling pathway. For example, a NF-κB stimulatory molecule that blocks the expression and or activity of an inhibitor of NF-κB signaling pathway is a genetic (e.g., siRNA, shRNA, gRNA, TALON, or Zn finger nuclease), chemical or biological inhibitor of A20. Other embodiments include NEMO-fusion constructs as NF-κB stimulatory molecules (e.g., hNEMO-FKBPx2, FKBPx2-hNEMO-L600 etc.). 
     As used herein a “non-naturally occurring agent” or “non-native” or “exogenous” refers to an agent that is not naturally expressed in a cell. Stated another way, the non-naturally occurring agent is “engineered” to be expressed in a cell. A non-naturally occurring agent may be a cloned version of a naturally occurring agent. Exemplary non-naturally occurring agents include CARs, SIRs, Ab-TCRs, TFPs, recombinant TCR, NEMO-K277A, vFLIP-K13 and K13-opt. A non-naturally occurring agent may be expressed into a cell using techniques of gene transfer known in the art, such as lentiviral or retroviral mediated gene transfer. A non-naturally occurring agent may be expressed in an immune cell using an exogenous promoter (e.g., EF1a promoter) or an endogenous promoter (e.g., TCRa promoter). When an endogenous gene (e.g., IKK1, IKK2, IKKy/NEMO) is cloned and ectopically expressed in a cell, it represents another example of a non-naturaly occurring agent. 
     As used herein a “non-naturally occurring immune receptor” or “exogenous immune receptor” refers to an immune receptor that is not naturally expressed in an immune cell. Stated another way, the non-naturally occurring immune receptor is “engineered” to be expressed in an immune cell. A non-naturally occurring immune receptor may be a cloned version of a naturally occurring immune receptor. Alternatively, a non-naturally occurring immune receptor may be a chimeric receptor that is produced using recombinant molecular biology techniques. Exemplary non-naturally occurring immune receptors include CARs, SIR, Ab-TCRs, TFPs and recombinant TCR. A non-naturally occurring immune receptor may be introduced into an immune cell using techniques of gene transfer known in the art, such as lentiviral or retroviral mediated gene transfer. A non-naturally occurring immune receptor may be expressed in an immune cell using an exogenous promoter (e.g., EFla promoter) or an endogenous promoter (e.g., TCRα promoter). 
     As used herein a “non-naturally occurring TCR antigen binding domain” or “exogenous TCR antigen binding domain” refers to a binding domain operably linked to a TCR constant region that is chimeric and non-naturally occurring with respect to a TCR present in nature. Stated another way, the non-naturally occurring TCR antigen binding domain is “engineered” using recombinant molecular biology techniques to be operably linked to a TCR and moreover, that the antigen binding domain is obtain or derived from a molecule that is distinct from a TCR found in nature. An antigen binding domain that is distinct from a TCR in nature includes antibody vH and vL fragments, humanized antibody fragments, chimeric antibody fragments, receptor ligands, and the like. 
     As used herein a “non-viral origin” refers to an agent (e.g., a protein) that is not wholly or in part encoded by a virus or has any domain or region of more than 10 amino acids (e.g, more than 15 amino acids, 20 amino acids, 25 amino acids or 50 amino acids) with greater than 80% (e.g., more than 85%, 90%, 95%, or 99%) sequence homology to a virally encoded protein. In an embodiment, an agent of non-viral origin is of human origin. In an embodiment, an agent of non-viral origin is a selective NF-κB activator. An exemplary agent of non-viral origin that is a selective NF-κB activator is human NEMO-K277A (SEQ ID NO: 4892). 
     The term “operably linked” or “functionally linked” refers to functional linkage or association between a first component and a second component such that each component can be functional. For example, operably linked includes the association between a regulatory sequence and a heterologous nucleic acid sequence resulting in expression of the latter. For example, a first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. In the context of two polypeptides that are operably linked a first polypeptide functions in the manner it would independent of any linkage and the second polypeptide functions as it would absent a linkage between the two. 
     “Percent identity” in the context of two or more nucleic acids or polypeptide sequences, refers to two or more sequences that are the same. Two sequences are “substantially identical” if two sequences have a specified percentage of amino acid residues or nucleotides that are the same (e.g., 60% identity, optionally 70%, 71%. 72%. 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%,81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity over a specified region, or, when not specified, over the entire sequence), when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the identity exists over a region that is at least about 50 nucleotides (or 10 amino acids) in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides (or 20, 50, 200 or more amino acids) in length. 
     For sequence comparison, generally one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. Methods of alignment of sequences for comparison are well known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman, (1970) Adv. Appl. Math. 2:482c, by the homology alignment algorithm of Needleman and Wunsch, (1970) J. Mol. Bioi. 48:443, by the search for similarity method of Pearson and Lipman, (1988) Proc. Nat&#39;l. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see, e.g., Brent et al., (2003) Current Protocols in Molecular Biology). 
     Two examples of algorithms that can be used for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., (1977) Nuc. Acids Res. 25:3389-3402; and Altschul et al., (1990) J. Mol. Bioi. 215:403-410, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. 
     The percent identity between two amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller, (1988) Comput. Appl. Biosci. 4:11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (1970) J. Mol. Bioi. 48:444-453) algorithm which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossom 62 matrix or a P AM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. 
     The term “polynucleotide”, “nucleic acid”, or “recombinant nucleic acid” refers to polymers of nucleotides such as deoxyribonucleic acid (DNA), and, where appropriate, ribonucleic acid (RNA). 
     A “protein” or “polypeptide”, which terms are used interchangeably herein, comprises one or more chains of chemical building blocks called amino acids that are linked together by chemical bonds called peptide bonds. 
     The term “retrovirus vector” refers to a vector derived from at least a portion of a retrovirus genome. Examples of retrovirus vector include MSCVneo, MSCV-pac (or MSCV-puro), MSCV-hygro as available from Addgene or Clontech. 
     The term “Sleeping Beauty Transposon” or “Sleeping Beauty Transposon Vector” refers to a vector derived from at least a portion of a Sleeping Beauty Transposon genome. 
     The term “single chain variable region” or “scFv” refers to a fusion protein comprising at least one antibody fragment comprising a variable region of a light chain and at least one antibody fragment comprising a variable region of a heavy chain, wherein the light and heavy chain variable regions are contiguously linked, e.g., via a synthetic linker, e.g., a short flexible polypeptide linker, and capable of being expressed as a single chain polypeptide, and wherein the scFv retains the specificity of the intact antibody from which it is derived. Unless specified, as used herein an scFv may have the vL and vH variable regions in either order, e.g., with respect to the N-terminal and C-terminal ends of the polypeptide, the scFv may comprise vL-linker-vH or may comprise vH-linker-vL. In this invention, a scFv is also described as vL-Gly-Ser-Linker-vH. Alternatively, a scFv is also described as (vL+vH) or (vH+vL). 
     The term “signaling domain” refers to the functional region of a protein which transmits information within the cell to regulate cellular activity via defined signaling pathways by generating second messengers or functioning as effectors by responding to such messengers. 
     The term “Synthetic Immune Receptor” or alternatively a “SIR” refers to a set of polypeptides, typically two in some embodiments, which when expressed in an effector cell, provides the cell with specificity for a target cell, typically a cancer cell, and with intracellular signal generation. SIRs represent next generaiton CAR platforms that are described in WO 2018/102795 A1 which is incorporated herein by reference. In a typical embodiment, a SIR comprises one or more antigen binding domains (e.g., antibody or antibody fragment, a ligand or a receptor) that bind to antigens as described herein, and are joined to one or more T cell receptor constant chains or regions via an optional linker. In some embodiments, the set of polypeptides are contiguous with each other. In some embodiments, a SIR comprises two or more sets of two or more polypeptides. The polypeptides of each set of SIR are contiguous with each other (functional polypeptide unit 1) but are not contiguous with the polypeptides of the other set (functional polypeptide unit 2). In some aspects, the T cell receptor constant chains (or regions) of the SIR is chosen from the constant chain of human T cell receptor-alpha (TCR-alpha or TCRα or TCRα or hTCR-alpha or hTCRα or hTCRα or Ca), human T cell receptor-betal(TCR-betal or TCRβ1 or TCRbl or hTCR-betal or hTCRβ1 or hTCRb1 or Cβ1), human T cell receptor-beta 2 (TCR-beta2 or TCRβ2 or TCRb2 or hTCR-beta2 or hTCRβ2 or hTCRb2 or Cβ2 also designated TCR-beta, TCRβ or TCRb or C(3), human Pre-T cell receptor alpha ((preTCR-alpha or preTCRα or preTCRα or preCα), human T cell receptor-gamma (TCR-gamma or TCRγ or TCRg or or hTCR-gamma or hTCRγ or hTCRg or hTCRγ1 or hTCRgammal, or Cγ), or human T cell receptor-delta (TCR-delta or TCRd or TCRδ or hTCR-delta or hTCRd or hTCRδ or Cδ). In some embodiments, the TCR constant chains of SIR are encoded by their wild-type nucleotide sequences while in other aspects the TCR constant chains of SIR are encoded by the nucleotide sequences that are not wild-type. In some embodiments, the TCR constant chains of SIR are encoded by their codon optimized sequences. In some embodiments, the TCR constant chains of SIR encode for the wild-type polypeptide sequences while in other embodiments the TCR constant chains of SIR encoded for polypeptides that carry one or more mutations. In some embodiments, the TCR constant chains of SIR are encoded by their codon optimized sequences that carry one or more mutations. A SIR that comprises an antigen binding domain (e.g., a scFv, or vHH) that targets a specific tumor maker “X”, such as those described herein, is also referred to as X-SIR or XSIR. For example, a SIR that comprises an antigen binding domain that targets CD19 is referred to as CD19-SIR or CD19SIR. The TCR constant chain/domain of a SIR can be derived from the same species in which the SIR will ultimately be used. For example, for use in humans, it may be beneficial for the TCR constant chain of the SIR to be derived from or comprised of human TCR constant chains. However, in some instances, it is beneficial for the TCR constant chain to be derived from the same species in which the SIR will ultimately be used in, but modified to carry amino acid substitutions that enhance the expression of the TCR constant chains. For example, for use in humans, it may be beneficial for the TCR constant chain of the SIR to be derived from or comprised of human TCR constant chains but in which certain amino acids are replaced by the corresponding amino acids from the murine TCR constant chains. Such murinized TCR constant chains provide increased expression of the SIR. The SIR or functional portion thereof, can include additional amino acids at the amino or carboxy terminus, or at both termini, which additional amino acids are not found in the amino acid sequence of the TCR or antigen binding domain which make up the SIR. Desirably, the additional amino acids do not interfere with the biological function of the SIR or functional portion, e.g., recognize target cells, detect cancer, treat or prevent cancer, etc. More desirably, the additional amino acids enhance the biological activity, as compared to the biological activity of the parent SIR. The nucleic acid and amio acid sequences of exemplary SIRs are provided in SEQ ID NO: 3878-3879 and in Tables 10-11. 
     The term “stimulation,” refers to a primary response induced by binding of a stimulatory molecule (e.g., a TCR/CD3 complex) with its cognate ligand (or target antigen) thereby mediating a signal transduction event, such as, but not limited to, signal transduction via the TCR/CD3. Stimulation can mediate altered expression of certain molecules. 
     The term “stimulatory molecule,” refers to a molecule expressed by an immune cell (e.g., T cell, NK cell, B cell) that provides the cytoplasmic signaling sequence(s) that regulate activation of the immune cell in a stimulatory way for at least some aspect of the immune cell signaling pathway. In one aspect, the signal is a primary signal that is initiated by, for instance, binding of a TCR/CD3 complex with an MHC molecule loaded with peptide, and which leads to mediation of a T cell response, including, but not limited to, proliferation, activation, differentiation, and the like. A primary cytoplasmic signaling sequence (also referred to as a “primary signaling domain”) that acts in a stimulatory manner may contain a signaling motif which is known as immunoreceptor tyrosine-based activation motif or ITAM. Examples of an ITAM containing cytoplasmic signaling sequence includes, but is not limited to, those derived from CD3 zeta, common FeR gamma (FCERIG), Fe gamma RIla, FeR beta (Fe Epsilon Rib), CD3 gamma, CD3 delta, CD3 epsilon, CD79a, CD79b, DAPIO, and DAP12. 
     The term “subject” is intended to include living organisms in which an immune response can be elicited (e.g., any domesticated mammals or a human). 
     “Switch domain,” or a “dimerization domain” as used herein, typically refers to a polypeptide-based entity that, in the presence of a dimerization molecule, associates with another switch domain. The association results in a functional coupling of a first entity linked to, e.g., fused to, a first switch domain, and a second entity linked to, e.g., fused to, a second switch domain. A first and second switch domain are collectively referred to as a dimerization switch. In embodiments, the first and second switch domains are the same as one another, e.g., they are polypeptides having the same primary amino acid sequence, and are referred to collectively as a homodimerization switch. In embodiments, the switch is intracellular. In embodiments, the switch domain is a polypeptide-based entity, e.g., FKBP (FK506 binding protein), and the dimerization molecule is small molecule, e.g., AP20187. 
     The terms “T-cell” and “T-lymphocyte” are interchangeable and used synonymously herein. Examples include but are not limited to naive T cells (“lymphocyte progenitors”), central memory T cells, effector memory T cells, stem memory T cells (Tscm), iPSC-derived T cells, synthetic T cells or combinations thereof. 
     The term “TCR-associated signaling module” refers to a molecule having a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM) that is part of the TCR-CD3 complex. TCR-associated signaling modules include CDyc, CD&amp; and CD3. 
     “Therapeutic agents” as used herein refers to agents that are used to, for example, treat, inhibit, prevent, mitigate the effects of, reduce the severity of, reduce the likelihood of developing, slow the progression of and/or cure, a disease. Diseases targeted by the therapeutic agents include but are not limited to infectious diseases, carcinomas, sarcomas, lymphomas, leukemia, germ cell tumors, blastomas, antigens expressed on various immune cells, and antigens expressed on cells associated with various hematologic diseases, and/or inflammatory diseases. 
     “Therapeutic Controls” as used herein refers to an element used for controlling the activity of a CAR expressing cell. In some embodiments, therapeutic controls for controlling the activity of the CAR expressing cells of the invention comprise any one or more of truncated epidermal growth factor receptor (tEGFR), truncated epidermal growth factor receptor viii (tEGFRviii), truncated CD30 (tCD30), truncated BCMA (tBCMass.), truncated CD19 (tCD19), thymidine kinase, cytosine deaminase, nitroreductase, xanthine-guanine phosphoribosyl transferase, human caspase 8, human caspase 9, inducible caspase 9, purine nucleoside phosphorylase, linamarase/linamarin/glucose oxidase, deoxyribonucleoside kinase, horseradish peroxidase (HRP)/indole-3-acetic (IAA), Gamma-glutamylcysteine synthetase, CD20/alphaCD20, CD34/thymidine kinase chimera, dox-depedent caspase-2, mutant thymidine kinase (HSV-TKSR39), AP1903/Fas system, a chimeric cytokine receptor (CCR), a selection marker, and combinations thereof. 
     The term “therapeutic effect” refers to a biological effect which can be manifested by various means, including but not limited to, e.g., decrease in tumor volume, a decrease in the number of cancer cells, a decrease in the number of metastases, an increase in life expectancy, decrease in cancer cell proliferation, decrease in cancer cell survival, decrease in the titer of the infectious agent, a decrease in colony counts of the infectious agent, amelioration of various physiological symptoms associated with a disease condition. A “therapeutic effect” can also be manifested by the ability of the peptides, polynucleotides, cells and antibodies in prevention of the occurrence of disease in the first place or in the prevention of relapse of the disease. 
     The term “therapeutically effective amount” as used herein refers to the amount of a pharmaceutical composition comprising one or more peptides as disclosed herein or a mutant, variant, analog or derivative thereof, to decrease at least one or more symptom of the disease or disorder, and relates to a sufficient amount of pharmacological composition to provide the desired effect. The phrase “therapeutically effective amount” as used herein means a sufficient amount of the composition to treat a disorder, at a reasonable benefit/risk ratio applicable to any medical treatment. 
     A therapeutically or prophylactically significant reduction in a symptom is, e.g. at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 125%, at least about 150% or more in a measured parameter as compared to a control or non-treated subject or the state of the subject prior to administering the oligopeptides described herein. Measured or measurable parameters include clinically detectable markers of disease, for example, elevated or depressed levels of a biological marker, as well as parameters related to a clinically accepted scale of symptoms or markers for diabetes. It will be understood, however, that the total daily usage of the compositions and formulations as disclosed herein will be decided by the attending physician within the scope of sound medical judgment. The exact amount required will vary depending on factors such as the type of disease being treated, gender, age, and weight of the subject. 
     The term “TCR receptor fusion proteins or TFP” refers to a next generation CAR platform as described in WO 2016/187349 A1 which is incorporated herein by reference. In an embodiment, a TFP comprises an antibody moiety that specifically binds to a target antigen fused to a TCR chain such as CD3ε, CD3γ, CD3δ, TCRα or TCRβ. Exemplary TCR chains that can be used in the construction of TFP are represented by SEQ ID NOs: 944-945, 948, 949-950 and 958 and are provided in WO 2017/070608 A1 which is incorporated herein by reference. A TFP incorporating CD3ε chain is referred to as a CD3ε TFP. A TFP incorporating CD3γ chain is referred to as a CD3γ TFP. A TFP incorporating CD3δ chain is referred to as a CD3δ TFP.The TFP incorporating CD3ε, CD3γ or CD3δ chains are collectively referred to as CD3ε/γ/δ TFP. Exemplary TFPs incorporating different antigen binding domains (e.g., vL and vH fragments, ligands, receptors etc.) described in this disclosure and co-expressing an accessory module encoding NEMO-K277A are provided in SEQ ID NO: 1900-3123 (Table 13). The SEQ ID Nos, antigen binding domains and target antigens of these TFPs can be determined by referring to Table 12 as these TFP constructs have identical antigen binding domains to the first generation CAR constructs coexpressing NEMO-K277A shown in Table 12 and are numbered in identical order. However, the accessory module encoding NEMO-K277A is optional. TFP with the antigen binding domains (i.e., vL and vH fragments, ligands and receptors etc.) described in this disclosure can be constructed without NEMO-K277A. As such, this accessory module along with the upstream Furine-SGSG-F2A sequence can be deleted from the TFPs represented by SEQ ID NO: 1900-3123. Alternatively, the accessory module encoding NEMO-K277A can be replaced by accessory modules encoding other signaling proteins, such as hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, or IKK1-S176E-S180E, and MyD88 —L265P, FKBPx2-NEMO, NEMO-L600-FKBPx2, and CMV-141 etc. 
     The term “transfer vector” refers to a composition of matter which comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Thus, the term “transfer vector” includes an autonomously replicating plasmid or a virus. The term should also be construed to further include non-plasmid and non-viral compounds which facilitate transfer of nucleic acid into cells, such as, for example, a poly lysine compound, liposome, and the like. Examples of viral transfer vectors include, but are not limited to, adenoviral vectors, adena-associated virus vectors, retroviral vectors, lentiviral vectors, and the like. 
     “Transmembrane domain” (TMD) as used herein refers to the region of the CAR which crosses the plasma membrane. The transmembrane domain of the CAR of the invention is the transmembrane region of a transmembrane protein (for example Type I transmembrane proteins), an artificial hydrophobic sequence or a combination thereof. Other transmembrane domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention. In some embodiments, the TMD encoded CAR comprising any of the backbones described herein comprises a transmembrane domain selected from the transmembrane domain of an alpha, beta or zeta chain of a T-cell receptor, CD3γ, CD3ε, CD3δ, CD28, CD45, CD4, CDS, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, KIRDS2, OX40, CD2, CD27, LFA-1 (CD1 la, CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD40, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), CD160, CD19, IL2R beta, IL2R gamma, IL7R a, ITGA1, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD1 ld, ITGAE, CD103, ITGAL, CD1 1a, LFA-1, ITGAM, CD1 1b, ITGAX, CD1 lc, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, DNAM1(CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRT AM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, PAG/Cbp, NKp44, NKp30, NKp46, NKG2D, and/or NKG2C. 
     As used herein “Tri-functional T cell antigen coupler or Tri-TAC” refer to a next generation CAR platform described in WO 2015/117229 A1, which is incorporated herein by reference. Tri-TAC targeting different antigens can be constructed using the antigen binding domains (e.g., vL and vH fragments, scFv, vHH, ligands and receptors etc.) described in this disclosure using techniques known in the art. Furthermore, the different accessory modules (e.g., NEMO-K277A, mNEMO-K270A etc.) described in this disclosure can be expressed in the Tri-TAC expressing immune cells, e.g., T cells, e.g., CAR-T cells. 
     As used herein, the terms “treat,” “treatment,” “treating,” or “amelioration” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a condition associated with, a disease or disorder. The term “treating” includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder, such as cancer. Treatment is generally “effective” if one or more symptoms or clinical markers are reduced. Alternatively, treatment is “effective” if the progression of a disease is reduced or halted. That is, “treatment” includes not just the improvement of symptoms or markers, but also a cessation of at least slowing of progress or worsening of symptoms that would be expected in absence of treatment. Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. The term “treatment” of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment). In some embodiments, treatment of cancer includes decreasing tumor volume, decreasing the number of cancer cells, inhibiting cancer metastases, increasing life expectancy, decreasing cancer cell proliferation, decreasing cancer cell survival, or amelioration of various physiological symptoms associated with the cancerous condition. 
     “Tumor,” as used herein refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. 
     “Vector”, “cloning vector” and “expression vector” as used herein refer to the vehicle by which a polynucleotide sequence (e.g. a foreign gene) can be introduced into a host cell, so as to transform the host and promote expression (e.g. transcription and translation) of the introduced sequence. Vectors include plasmids, phages, viruses, etc. 
     The term “zeta” or alternatively “zeta chain”, “CD3-zeta” or “TCR-zeta” is defined as the protein provided as GenBan Ace. No. BAG36664.1, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like, and a “zeta stimulatory domain” or alternatively a “CD3-zeta stimulatory domain” or a “TCR-zeta stimulatory domain” is defined as the amino acid residues from the cytoplasmic domain of the zeta chain, or functional derivatives thereof, that are sufficient to functionally transmit an initial signal necessary forT cell activation. In one aspect the cytoplasmic domain of zeta comprises residues 52 through 164 of GenBank Ace. No. BAG36664.1 or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like, that are functional orthologs thereof. In one aspect, the “zeta stimulatory domain” or a “CD3-zeta stimulatory domain” is the sequence provided as SEQ ID NO: 4853 (Table 6D). 
     The binding domain of the CAR is selected to bind to a desired epitope. For example, the epitope recognized by a CAR can be also determined from the epitope recognized by the scFv comprising the CAR. For example, since the antigen specific domain of the CAR CD8SP-MPL-161-(vL-vH)-Myc-BBz-T2A-PAC (SEQ ID NO: 1509 and SEQ ID NO: 5422) targeting MPL is comprised of scFv MPL-161-(vL-vH) (SEQ ID NO: 808 and SEQ ID NO: 4721), it is expected that the CAR would target the same epitope as the scFv and the parental antibody from which the scFv is derived. The epitope recognized by the scFv MPL-161-(vL-vH) (SEQ ID NO: 808 and SEQ ID NO: 4721) is provided in SEQ ID NO: 15160. The epitopes recognized by several scFv and/or their parental antibodies used in the construction of the CARs and backbones of this dislcosure are known in the art. Alternatively, the epitope targeted by a CAR (including the CARs that are present as parat of backbones) can be determined by generating a series of mutants of its target antigen and testing the ability of the mutants to bind to the CAR-expressing cells. As an example, the epitope recognized by the CAR CD8SP-MPL-161-(vL-vH)-Myc-BBz-T2A-PAC targeting MPL can be determined by generating a panel of mutants of the MPL-ECD-GGSG-Nluc-AcV5 fusion construct (DNA SEQ ID NO: 1015 and PRT SEQ ID NO: 4928). The mutant constructs would be transfected into a suitable cell line (e.g., 293FT cells) and the supernatant containing the fusion protein collected and assayed for NLuc activity to assure that the different mutant MPL-ECD-GGSG-Nluc-AcV5 fusion proteins are being secreted in the supernatant. Subsequently, the fusion proteins would be tested for their ability to bind to cells (e.g., Jurkat cells or T cells) expressing the CD8SP-MPL-161-(vL-vH)-Myc-BBz-T2A-PAC CAR construct. The mutant that fails to bind to the CAR-expressing cells is a candidate for containing the epitope targeted by the MPL-specific CAR. An alternate approach to determine the epitope recognized by a particular CAR could include a functional competitive assay with different test antibodies. For example, T cells expressing the CD8SP-MPL-161-(vL-vH)-Myc-BBz-T2A-PAC CAR could be co-cultured with a cell line expressing MPL (e.g., HEL cells) in the absence and presence of increasing concentrations of different test MPL antibodies. In case the epitope recognized by a test MPL antibody overlaps with the epitope recognized by the CD8SP-MPL-161-(vL-vH)-Myc-BBz-T2A-PAC CAR, then the test antibody would be expected to block target-cell killing and cytokine production induced by T cells expressing the CD8SP-MPL-161-(vL-vH)-Myc-BBz-T2A-PAC CAR in a dose-dependent manner. A non-specific antibody of the same isotype as the test antibody would be included as a control and would be expected to have no effect on the target-cell killing and cytokine production induced by T cells expressing the CAR. Similarly, a specific CAR can be expressed in Jurkat-NFAT-EGFP cells and the ability of a test antibody to block EGFP induction by the CAR-expressing Jurkat-NFAT-GFP cells upon coculture with a target cell line can be used to determine whether the epitope recognized by the test antibody overlaps with the epitope recognized by the said CAR. 
     Also provided herein are compositions comprising a non-naturally occurring immune receptor, e.g., a CAR, and an accessory module (including NF-κB stimulatory molecules and selective NF-κB activators) and method of using same to treat diseases, including cancer. As described herein, specific combinations of conventional CARs (Table 1) and accessory modules as described in Table 2 are provided. 
     Table 1: Conventional CAR architectures. First generation conventional CARs (Conventional CAR I) have an intracellular signaling (ISD) domain (e.g. CD3z) and no costimulatory domain. The TCR fusion proteins (TFP) are another example of conventional CAR 1. Second generation conventional CARs (Conventional CAR 2 or CAR II) have one costimulatory domain (e.g. 41BB or CD28) and an intracellular signaling (ISD) domain (e.g. CD3z). Third generation conventional CARs (Conventional CAR 3 or CAR III) have two costimulatory domains (e.g. 41BB and CD28) and an intracellular signaling (ISD) domain (e.g. CD3z). Ab-TCRs are duel chain receptors and have been described in PCT/US2016/058305. cTCRs are single chain, one-and-half, or double chain receptors consisting of antigen binding domain derived from a vL and vH fragment that are fused to one or more TCR constant chain and result in activation of T cell signaling. Synthetic immune receptors are next generation CARs and are described in U.S. 62/429,597 and WO 2018/102795 A1: 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Conventional CAR Architectures 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 1 
                 CAR 1 or CAR I 
                 ASD 
                 HR 
                 TMD 
                 ISD 
                   
                   
               
               
                   
                 (including TFP) 
               
               
                 2 
                 CAR 2 (CAR II) 
                 ASD 
                 HR 
                 TMD 
                 CSD 
                 ISD 
               
               
                 3 
                 CAR 3 (CAR III) 
                 ASD 
                 HR 
                 TMD 
                 CSD-I 
                 CSD-II 
                 ISD 
               
               
                 4 
                 Ab-TCR 
                 vL-cL 
                 TCRD(1) 
                 2A 
                 vH-CH1 
                 TCRD (II) 
               
               
                 5 
                 Double Chain 
                 vL 
                 TCR-C(1) 
                 2A 
                 vH 
                 TCR-C (II) 
               
               
                   
                 cTCR/SIR-1 
               
               
                 6 
                 One &amp; Half 
                   
                 TCR-C(1) 
                 2A 
                 ASD 
                 TCR-C (II) 
               
               
                   
                 Chain cTCR/SIR- 
               
               
                   
                 3 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Exemplary Backbones 
               
            
           
           
               
               
            
               
                   
                 Accessory Module 
               
            
           
           
               
               
               
               
               
            
               
                   
                 CAR 
                   
                 SEQ ID 
                 SEQ ID 
               
               
                 Backbone No. 
                 Component 
                 NAME 
                 (DNA) 
                 (PRT) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Backbone 1 
                 CAR I 
                 K13-vFLIP 
                 972 
                 4885 
               
               
                 Backbone 2 
                 CAR I 
                 hNEMO-K277A 
                 979 
                 4892 
               
               
                 Backbone 3 
                 CAR I 
                 FKBPx2-hNEMO-K277A 
                 1006 
                 4919 
               
               
                 Backbone 4 
                 CAR I 
                 FKBPx2-hNEMO-L753(251) 
                 1007 
                 4920 
               
               
                 Backbone 5 
                 CAR I 
                 FKBPx2-hNEMO-L600(200) 
                 1008 
                 4921 
               
               
                 Backbone 6 
                 CAR I 
                 FKBPx2-RIP-ID 
                 1009 
                 4922 
               
               
                 Backbone 7 
                 CAR I 
                 IKK2-S177E-S181E 
                 1002 
                 4915 
               
               
                 Backbone 8 
                 CAR I 
                 IKK1-S176E-S180E 
                 1004 
                 4917 
               
               
                 Backbone 9 
                 CAR I 
                 MYD88-L265P 
                 1000 
                 4913 
               
               
                 Backbone 10 
                 CAR I 
                 TCL-1A 
                 1005 
                 4918 
               
               
                 Backbone 11 
                 CAR I 
                 IgSP-[hTRAC-opt2] 
                 1010 
                 4923 
               
               
                 Backbone 12 
                 CAR I 
                 IgSP-[hTRBC-opt2] 
                 1011 
                 4924 
               
               
                 Backbone 13 
                 CAR II 
                 K13-vFLIP 
                 972 
                 4885 
               
               
                 Backbone 14 
                 CAR II 
                 hNEMO-K277A 
                 979 
                 4892 
               
               
                 Backbone 15 
                 CAR II 
                 FKBPx2-hNEMO-K277A 
                 1006 
                 4919 
               
               
                 Backbone 16 
                 CAR II 
                 FKBPx2-hNEMO-L753(251) 
                 1007 
                 4920 
               
               
                 Backbone 17 
                 CAR II 
                 FKBPx2-hNEMO-L600(200) 
                 1008 
                 4921 
               
               
                 Backbone 18 
                 CAR II 
                 FKBPx2-RIP-ID 
                 1009 
                 4922 
               
               
                 Backbone 19 
                 CAR II 
                 IKK2-S177E-S181E 
                 1002 
                 4915 
               
               
                 Backbone 20 
                 CAR II 
                 IKK1-S176E-S180E 
                 1004 
                 4917 
               
               
                 Backbone 21 
                 CAR II 
                 MYD88-L265P 
                 1000 
                 4913 
               
               
                 Backbone 22 
                 CAR II 
                 TCL-1A 
                 1005 
                 4918 
               
               
                 Backbone 23 
                 CAR II 
                 IgSP-[hTRAC-opt2] 
                 1010 
                 4923 
               
               
                 Backbone 24 
                 CAR II 
                 IgSP-[hTRBC-opt2] 
                 1011 
                 4924 
               
               
                 Backbone 25 
                 CAR III 
                 K13-vFLIP 
                 972 
                 4885 
               
               
                 Backbone 26 
                 CAR III 
                 hNEMO-K277A 
                 979 
                 4892 
               
               
                 Backbone 27 
                 CAR III 
                 FKBPx2-hNEMO-K277A 
                 1006 
                 4919 
               
               
                 Backbone 28 
                 CAR III 
                 FKBPx2-hNEMO-L753(251) 
                 1007 
                 4920 
               
               
                 Backbone 29 
                 CAR III 
                 FKBPx2-hNEMO-L600(200) 
                 1008 
                 4921 
               
               
                 Backbone 30 
                 CAR III 
                 FKBPx2-RIP-ID 
                 1009 
                 4922 
               
               
                 Backbone 31 
                 CAR III 
                 IKK2-S177E-S181E 
                 1002 
                 4915 
               
               
                 Backbone 32 
                 CAR III 
                 IKK1-S176E-S180E 
                 1004 
                 4917 
               
               
                 Backbone 33 
                 CAR III 
                 MYD88-L265P 
                 1000 
                 4913 
               
               
                 Backbone 34 
                 CAR III 
                 TCL-1A 
                 1005 
                 4918 
               
               
                 Backbone 35 
                 CAR III 
                 IgSP-[hTRAC-opt2] 
                 1010 
                 4923 
               
               
                 Backbone 36 
                 CAR III 
                 IgSP-[hTRBC-opt2] 
                 1011 
                 4924 
               
               
                 Backbone 37 
                 Ab-TCR 
                 K13-vFLIP 
                 972 
                 4885 
               
               
                 Backbone 38 
                 Ab-TCR 
                 hNEMO-K277A 
                 979 
                 4892 
               
               
                 Backbone 39 
                 Ab-TCR 
                 FKBPx2-hNEMO-K277A 
                 1006 
                 4919 
               
               
                 Backbone 40 
                 Ab-TCR 
                 FKBPx2-hNEMO-L753(251) 
                 1007 
                 4920 
               
               
                 Backbone 41 
                 Ab-TCR 
                 FKBPx2-hNEMO-L600(200) 
                 1008 
                 4921 
               
               
                 Backbone 42 
                 Ab-TCR 
                 FKBPx2-RIP-ID 
                 1009 
                 4922 
               
               
                 Backbone 43 
                 Ab-TCR 
                 IKK2-S177E-S181E (IKK2-SS/EE) 
                 1002 
                 4915 
               
               
                 Backbone 44 
                 Ab-TCR 
                 IKK1-S176E-S180E IKK1-SS/EE) 
                 1004 
                 4917 
               
               
                 Backbone 45 
                 Ab-TCR 
                 MYD88-L265P 
                 1000 
                 4913 
               
               
                 Backbone 46 
                 Ab-TCR 
                 TCL-1A 
                 1005 
                 4918 
               
               
                 Backbone 47 
                 Ab-TCR 
                 IgSP-[hTRAC-opt2] 
                 1010 
                 4923 
               
               
                 Backbone 48 
                 Ab-TCR 
                 IgSP-[hTRBC-opt2] 
                 1011 
                 4924 
               
               
                 Backbone 49 
                 DC-cTCR/SIR 
                 K13-vFLIP 
                 972 
                 4885 
               
               
                 Backbone 50 
                 DC-cTCR/SIR 
                 hNEMO-K277A 
                 979 
                 4892 
               
               
                 Backbone 51 
                 DC-cTCR/SIR 
                 FKBPx2-hNEMO-K277A 
                 1006 
                 4919 
               
               
                 Backbone 52 
                 DC-cTCR/SIR 
                 FKBPx2-hNEMO-L753(251) 
                 1007 
                 4920 
               
               
                 Backbone 53 
                 DC-cTCR/SIR 
                 FKBPx2-hNEMO-L600(200) 
                 1008 
                 4921 
               
               
                 Backbone 54 
                 DC-cTCR/SIR 
                 FKBPx2-RIP-ID 
                 1009 
                 4922 
               
               
                 Backbone 55 
                 DC-cTCR/SIR 
                 IKK2-S177E-S181E 
                 1002 
                 4915 
               
               
                 Backbone 56 
                 DC-cTCR/SIR 
                 IKK1-S176E-S180E 
                 1004 
                 4917 
               
               
                 Backbone 57 
                 DC-cTCR/SIR 
                 MYD88-L265P 
                 1000 
                 4913 
               
               
                 Backbone 58 
                 DC-cTCR/SIR 
                 TCL-1A 
                 1005 
                 4918 
               
               
                 Backbone 59 
                 DC-cTCR/SIR 
                 IgSP-[hTRAC-opt2] 
                 1010 
                 4923 
               
               
                 Backbone 60 
                 DC-cTCR/SIR 
                 IgSP-[hTRBC-opt2] 
                 1011 
                 4924 
               
               
                 Backbone 61 
                 OHC-cTCR/SIR 
                 K13-vFLIP 
                 972 
                 4885 
               
               
                 Backbone 62 
                 OHC-cTCR/SIR 
                 hNEMO-K277A 
                 979 
                 4892 
               
               
                 Backbone 63 
                 OHC-cTCR/SIR 
                 FKBPx2-hNEMO-K277A 
                 1006 
                 4919 
               
               
                 Backbone 64 
                 OHC-cTCR/SIR 
                 FKBPx2-hNEMO-L753(251) 
                 1007 
                 4920 
               
               
                 Backbone 65 
                 OHC-cTCR/SIR 
                 FKBPx2-hNEMO-L600(200) 
                 1008 
                 4921 
               
               
                 Backbone 66 
                 OHC-cTCR/SIR 
                 FKBPx2-RIP-ID 
                 1009 
                 4922 
               
               
                 Backbone 67 
                 OHC-cTCR/SIR 
                 IKK2-S177E-S181E 
                 1002 
                 4915 
               
               
                 Backbone 68 
                 OHC-cTCR/SIR 
                 IKK1-S176E-S180E 
                 1004 
                 4917 
               
               
                 Backbone 69 
                 OHC-cTCR/SIR 
                 MYD88-L265P 
                 1000 
                 4913 
               
               
                 Backbone 70 
                 OHC-cTCR/SIR 
                 TCL-1A 
                 1005 
                 4918 
               
               
                 Backbone 71 
                 OHC-cTCR/SIR 
                 IgSP-[hTRAC-opt2] 
                 1010 
                 4923 
               
               
                 Backbone 72 
                 OHC-cTCR/SIR 
                 IgSP-[hTRBC-opt2] 
                 1011 
                 4924 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6A 
               
             
            
               
                   
               
               
                 TARGET ANTIGENS, NAMES AND SEQ IDs OF vL 
               
               
                 FRAGMENTS AND SEQ IDs of CDR1-3 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 SEQ 
                 SEQ 
                 SEQ 
                 SEQ 
                 SEQ 
               
               
                   
                   
                 ID vL 
                 ID vL 
                 ID-vL 
                 ID-vL 
                 ID-vL 
               
               
                 TARGET 
                 NAME of vL 
                 (DNA) 
                 (PRT) 
                 CDR1 
                 CDR2 
                 CDR3 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 ALK 
                 Alk-48-vL 
                 7792 
                 10553 
                 13204 
                 13510 
                 13816 
               
               
                 ALK 
                 Alk-58-vL 
                 7793 
                 10554 
                 13205 
                 13511 
                 13817 
               
               
                 Amyloid 
                 Amyloid-158-vL 
                 7794 
                 10555 
                 13206 
                 13512 
                 13818 
               
               
                 BCMA 
                 BCMA-ET-40-vL 
                 7795 
                 10556 
                 13207 
                 13513 
                 13819 
               
               
                 BCMA 
                 BCMA-ET-54-vL 
                 7796 
                 10557 
                 13208 
                 13514 
                 13820 
               
               
                 BCMA 
                 BCMA-huC12A3-vL 
                 7797 
                 10558 
                 13209 
                 13515 
                 13821 
               
               
                 BCMA 
                 BCMA-J6M0-vL 
                 7798 
                 10559 
                 13210 
                 13516 
                 13822 
               
               
                 CCR4 
                 CCR4-humAb1567- 
                 7799 
                 10560 
                 13211 
                 13517 
                 13823 
               
               
                   
                 vL 
               
               
                 CD123 
                 CD123-CSL362-vL 
                 7800 
                 10561 
                 13212 
                 13518 
                 13824 
               
               
                 CD138 
                 CD138-vL 
                 7801 
                 10562 
                 13213 
                 13519 
                 13825 
               
               
                 CD179b 
                 CD179b-vL 
                 7802 
                 10563 
                 13214 
                 13520 
                 13826 
               
               
                 CD19 
                 CD19-4G7-vL 
                 7803 
                 10564 
                 13215 
                 13521 
                 13827 
               
               
                 CD19 
                 CD19Bu12-vL 
                 7804 
                 10565 
                 13216 
                 13522 
                 13828 
               
               
                 CD19 
                 CD19MM-vL 
                 7805 
                 10566 
                 13217 
                 13523 
                 13829 
               
               
                 CD19 
                 FMC63-vL 
                 7806 
                 10567 
                 13218 
                 13524 
                 13830 
               
               
                 CD19 
                 FMC63-[2]-vL 
                 7807 
                 10568 
                 13219 
                 13525 
                 13831 
               
               
                 CD19 
                 FMC63-[3]-vL 
                 7808 
                 10569 
                 13220 
                 13526 
                 13832 
               
               
                 CD19 
                 huFMC63-11-vL 
                 7809 
                 10570 
                 13221 
                 13527 
                 13833 
               
               
                 CD20 
                 CD20-2F2-vL 
                 7810 
                 10571 
                 13222 
                 13528 
                 13834 
               
               
                 CD20 
                 CD20-GA101-vL 
                 7811 
                 10572 
                 13223 
                 13529 
                 13835 
               
               
                 CD22 
                 CD22-h10F4-vL 
                 7812 
                 10573 
                 13224 
                 13530 
                 13836 
               
               
                 CD22 
                 CD22- 
                 7813 
                 10574 
                 13225 
                 13531 
                 13837 
               
               
                   
                 H22Rhov2ACDRKA- 
               
               
                   
                 vL 
               
               
                 CD22 
                 CD22m971-vL 
                 7814 
                 10575 
                 13226 
                 13532 
                 13838 
               
               
                 CD276 
                 CD276-17-vL 
                 7815 
                 10576 
                 13227 
                 13533 
                 13839 
               
               
                 CD30 
                 CD30-5F11-vL 
                 7816 
                 10577 
                 13228 
                 13534 
                 13840 
               
               
                 CD30 
                 CD30-Ac10-vL 
                 7817 
                 10578 
                 13229 
                 13535 
                 13841 
               
               
                 CD32 
                 CD32-Med9-vL 
                 7818 
                 10579 
                 13230 
                 13536 
                 13842 
               
               
                 CD324 
                 CD324-hSC10-17-vL 
                 7819 
                 10580 
                 13231 
                 13537 
                 13843 
               
               
                 CD324 
                 CD324-SC10-6-vL 
                 7820 
                 10581 
                 13232 
                 13538 
                 13844 
               
               
                 CD33 
                 CD33-huMyc9-vL 
                 7821 
                 10582 
                 13233 
                 13539 
                 13845 
               
               
                 CD33 
                 CD33-AF5-vL 
                 7822 
                 10583 
                 13234 
                 13540 
                 13846 
               
               
                 CD34 
                 CD34-hu4C7-[2]-vL 
                 7823 
                 10584 
                 13235 
                 13541 
                 13847 
               
               
                 CD34 
                 CD34-hu4C7-vL 
                 7824 
                 10585 
                 13236 
                 13542 
                 13848 
               
               
                 CD44v6 
                 CD44v6-Biwa8-vL 
                 7825 
                 10586 
                 13237 
                 13543 
                 13849 
               
               
                 CD5 
                 CD5-18-vL 
                 7826 
                 10587 
                 13238 
                 13544 
                 13850 
               
               
                 CD5 
                 CD5-9-vL 
                 7827 
                 10588 
                 13239 
                 13545 
                 13851 
               
               
                 CD70 
                 CD70-h1F6-vL 
                 7828 
                 10589 
                 13240 
                 13546 
                 13852 
               
               
                 CD79b 
                 CD79b-2F2-vL 
                 7829 
                 10590 
                 13241 
                 13547 
                 13853 
               
               
                 CD79b 
                 huMA79bv28-vL 
                 7830 
                 10591 
                 13242 
                 13548 
                 13854 
               
               
                 CDH17 
                 CDH17-PTA001A4- 
                 7831 
                 10592 
                 13243 
                 13549 
                 13855 
               
               
                   
                 vL 
               
               
                 CDH19 
                 CDH19-16A4-vL 
                 7832 
                 10593 
                 13244 
                 13550 
                 13856 
               
               
                 CDH6 
                 CDH6-NOV710-vL 
                 7833 
                 10594 
                 13245 
                 13551 
                 13857 
               
               
                 CDH6 
                 CDH6-NOV712-vL 
                 7834 
                 10595 
                 13246 
                 13552 
                 13858 
               
               
                 CLEC5A 
                 CLEC5A-3E12A2- 
                 7835 
                 10596 
                 13247 
                 13553 
                 13859 
               
               
                   
                 vL 
               
               
                 CLEC5A 
                 CLEC5A-8H8F5-vL 
                 7836 
                 10597 
                 13248 
                 13554 
                 13860 
               
               
                 CLL1 
                 CLL1-M26-vL 
                 7837 
                 10598 
                 13249 
                 13555 
                 13861 
               
               
                 CLL1 
                 CLL1-M32-vL 
                 7838 
                 10599 
                 13250 
                 13556 
                 13862 
               
               
                 CMVpp65/MHC 
                 CMVpp65-F5-vL 
                 7839 
                 10600 
                 13251 
                 13557 
                 13863 
               
               
                 class I 
               
               
                 CS1 
                 huLuc63-vL 
                 7840 
                 10601 
                 13252 
                 13558 
                 13864 
               
               
                 CS1 
                 HuLuc64-[2]-vL 
                 7841 
                 10602 
                 13253 
                 13559 
                 13865 
               
               
                 CS1 
                 HuLuc64-vL 
                 7842 
                 10603 
                 13254 
                 13560 
                 13866 
               
               
                 CS1 
                 huLuc90-vL 
                 7843 
                 10604 
                 13255 
                 13561 
                 13867 
               
               
                 CSF2RA 
                 CSF2RA-Ab1-vL 
                 7844 
                 10605 
                 13256 
                 13562 
                 13868 
               
               
                 CSF2RA 
                 CSF2RA-Ab6-vL 
                 7845 
                 10606 
                 13257 
                 13563 
                 13869 
               
               
                 DLL3 
                 DLL3-hSC16-13-vL 
                 7846 
                 10607 
                 13258 
                 13564 
                 13870 
               
               
                 DLL3 
                 DLL3-hSC16-56-vL 
                 7847 
                 10608 
                 13259 
                 13565 
                 13871 
               
               
                 EBNA3c/MHC 
                 EBNA3c-315-vL 
                 7848 
                 10609 
                 13260 
                 13566 
                 13872 
               
               
                 class I 
               
               
                 EGFR 
                 Cetuximab-vL 
                 7849 
                 10610 
                 13261 
                 13567 
                 13873 
               
               
                 EGFR 
                 Nimotuzumab-vL 
                 7850 
                 10611 
                 13262 
                 13568 
                 13874 
               
               
                 EGFRviii 
                 EGFRviii-139-vL 
                 7851 
                 10612 
                 13263 
                 13569 
                 13875 
               
               
                 EGFRviii 
                 EGFRviii-2173-vL 
                 7852 
                 10613 
                 13264 
                 13570 
                 13876 
               
               
                 EpCam1 
                 EpCam1-D5K5-vL 
                 7853 
                 10614 
                 13265 
                 13571 
                 13877 
               
               
                 EpCam1 
                 Epcam1-MM1-vL 
                 7854 
                 10615 
                 13266 
                 13572 
                 13878 
               
               
                 FITC 
                 FITC-vL 
                 7855 
                 10616 
                 13267 
                 13573 
                 13879 
               
               
                 FLT3 
                 FLT3-NC7-vL 
                 7856 
                 10617 
                 13268 
                 13574 
                 13880 
               
               
                 HIV1-envelop 
                 HIV1-N6-vL 
                 7857 
                 10618 
                 13269 
                 13575 
                 13881 
               
               
                 glycoprotein 
               
               
                 Folate Receptor 
                 FR1-huMov19-vL 
                 7858 
                 10619 
                 13270 
                 13576 
                 13882 
               
               
                 1 (FR1) 
               
               
                 GAD 
                 GAD-G3H8-vL 
                 7859 
                 10620 
                 13271 
                 13577 
                 13883 
               
               
                 GD2 
                 GD2-hu14-18-vL 
                 7860 
                 10621 
                 13272 
                 13578 
                 13884 
               
               
                 GD2 
                 GD2-hu3F8-vL 
                 7861 
                 10622 
                 13273 
                 13579 
                 13885 
               
               
                 GD3 
                 GD3-KM-641-vL 
                 7862 
                 10623 
                 13274 
                 13580 
                 13886 
               
               
                 GFRa4 
                 GFRa4-P4-10-2-vL 
                 7863 
                 10624 
                 13275 
                 13581 
                 13887 
               
               
                 GFRa4 
                 GFRa4-P4-10-vL 
                 7864 
                 10625 
                 13276 
                 13582 
                 13888 
               
               
                 GFRa4 
                 GFRAlpha4-P4-6-vL 
                 7865 
                 10626 
                 13277 
                 13583 
                 13889 
               
               
                 GM1 
                 GMl-5B2-vL 
                 7866 
                 10627 
                 13278 
                 13584 
                 13890 
               
               
                 GM1 
                 GM1-7E5-vL 
                 7867 
                 10628 
                 13279 
                 13585 
                 13891 
               
               
                 gp100/MHC 
                 gp100-G2D12-vL 
                 7868 
                 10629 
                 13280 
                 13586 
                 13892 
               
               
                 class I 
               
               
                 gp100/MHC 
                 gp100-vL 
                 7869 
                 10630 
                 13281 
                 13587 
                 13893 
               
               
                 class I 
               
               
                 GPC3 
                 GPC3-4E5-vL 
                 7870 
                 10631 
                 13282 
                 13588 
                 13894 
               
               
                 gpNMB 
                 gpNMB-115-vL 
                 7871 
                 10632 
                 13283 
                 13589 
                 13895 
               
               
                 GPRC5D 
                 GPRC5D-ET150-18- 
                 7872 
                 10633 
                 13284 
                 13590 
                 13896 
               
               
                   
                 vL 
               
               
                 GPRC5D 
                 GPRC5D-ET150-5- 
                 7873 
                 10634 
                 13285 
                 13591 
                 13897 
               
               
                   
                 vL 
               
               
                 Her2 
                 Her2-Hu4D5-vL 
                 7874 
                 10635 
                 13286 
                 13592 
                 13898 
               
               
                 HIV1-gag (77- 
                 HIV1-E5-vL 
                 7875 
                 10636 
                 13287 
                 13593 
                 13899 
               
               
                 85)/MHC 
               
               
                 HIV1-envelop 
                 HIV1-3BNC117-vL 
                 7876 
                 10637 
                 13288 
                 13594 
                 13900 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-PGT-128-vL 
                 7877 
                 10638 
                 13289 
                 13595 
                 13901 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-VR-C01-vL 
                 7878 
                 10639 
                 13290 
                 13596 
                 13902 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-X5-vL 
                 7879 
                 10640 
                 13291 
                 13597 
                 13903 
               
               
                 glycoprotein 
               
               
                 HMW-MAA 
                 HMW-MAA-hIND- 
                 7880 
                 10641 
                 13292 
                 13598 
                 13904 
               
               
                   
                 vL 
               
               
                 HTLV1- 
                 TAX-T3E3-vL 
                 7881 
                 10642 
                 13293 
                 13599 
                 13905 
               
               
                 TAX/MHC class 
               
               
                 I 
               
               
                 HTLV1- 
                 TAX-T3F2-vL 
                 7882 
                 10643 
                 13294 
                 13600 
                 13906 
               
               
                 TAX/MHC class 
               
               
                 I 
               
               
                 IL11Ra 
                 IL11Ra-8E2-vL 
                 7883 
                 10644 
                 13295 
                 13601 
                 13907 
               
               
                 IL13Ra2 
                 IL13Ra2-hu107-vL 
                 7884 
                 10645 
                 13296 
                 13602 
                 13908 
               
               
                 IL13Ra2 
                 IL13Ra2-Hu108-vL 
                 7885 
                 10646 
                 13297 
                 13603 
                 13909 
               
               
                 IL6R 
                 IL6R-M83-vL 
                 7886 
                 10647 
                 13298 
                 13604 
                 13910 
               
               
                 Influenza A HA 
                 FLU-MEDI-8852-vL 
                 7887 
                 10648 
                 13299 
                 13605 
                 13911 
               
               
                 KSHV-gH 
                 YC15-vL 
                 7888 
                 10649 
                 13300 
                 13606 
                 13912 
               
               
                 KSHV-K8.1 
                 4C3-vL 
                 7889 
                 10650 
                 13301 
                 13607 
                 13913 
               
               
                 L1CAM 
                 L1CAM-9-3-HU3-vL 
                 7890 
                 10651 
                 13302 
                 13608 
                 13914 
               
               
                 LAMP1 
                 LAMP1-humab 1-2- 
                 7891 
                 10652 
                 13303 
                 13609 
                 13915 
               
               
                   
                 vL 
               
               
                 LAMP1 
                 LAMP1-Mb4-vL 
                 7892 
                 10653 
                 13304 
                 13610 
                 13916 
               
               
                 LewisY 
                 LewisY-huS193-vL 
                 7893 
                 10654 
                 13305 
                 13611 
                 13917 
               
               
                 Lym1 
                 Lym1-vL 
                 7894 
                 10655 
                 13306 
                 13612 
                 13918 
               
               
                 Lym2 
                 Lym2-vL 
                 7895 
                 10656 
                 13307 
                 13613 
                 13919 
               
               
                 MART1/MHC 
                 MART1-CAG10-vL 
                 7896 
                 10657 
                 13308 
                 13614 
                 13920 
               
               
                 class I 
               
               
                 MART1/MHC 
                 MART1-CLA12-vL 
                 7897 
                 10658 
                 13309 
                 13615 
                 13921 
               
               
                 class I 
               
               
                 Mesothelin 
                 Mesothelin-m912-vL 
                 7898 
                 10659 
                 13310 
                 13616 
                 13922 
               
               
                 MPL (TPO-R) 
                 MPL-111-vL 
                 7899 
                 10660 
                 13311 
                 13617 
                 13923 
               
               
                 MPL (TPO-R) 
                 MPL-161-HL-vL 
                 7900 
                 10661 
                 13312 
                 13618 
                 13924 
               
               
                 MPL (TPO-R) 
                 MPL-161-vL 
                 7901 
                 10662 
                 13313 
                 13619 
                 13925 
               
               
                 MPL (TPO-R) 
                 MPL-175-vL 
                 7902 
                 10663 
                 13314 
                 13620 
                 13926 
               
               
                 MPL (TPO-R) 
                 MPL-178-vL 
                 7903 
                 10664 
                 13315 
                 13621 
                 13927 
               
               
                 MPL (TPO-R) 
                 MPL-huVB22Bw5- 
                 7904 
                 10665 
                 13316 
                 13622 
                 13928 
               
               
                   
                 vL 
               
               
                 MPL (TPO-R) 
                 MPL-12E10-vL 
                 7905 
                 10666 
                 13317 
                 13623 
                 13929 
               
               
                 MPL (TPO-R) 
                 MPL-AB317-vL 
                 7906 
                 10667 
                 13318 
                 13624 
                 13930 
               
               
                 Muc1/MHC 
                 MUC1-D6-M3A1-vL 
                 7907 
                 10668 
                 13319 
                 13625 
                 13931 
               
               
                 class I 
               
               
                 Muc1/MHC 
                 Muc1-D6-M3B8-vL 
                 7908 
                 10669 
                 13320 
                 13626 
                 13932 
               
               
                 class I 
               
               
                 Muc16 
                 Muc16-4H11-vL 
                 7909 
                 10670 
                 13321 
                 13627 
                 13933 
               
               
                 NKG2D 
                 NKG2D-MS-vL 
                 7910 
                 10671 
                 13322 
                 13628 
                 13934 
               
               
                 NYBR1 
                 NYBR1-vL 
                 7911 
                 10672 
                 13323 
                 13629 
                 13935 
               
               
                 NY-ESO/MHC 
                 NY-ESO-T1-vL 
                 7912 
                 10673 
                 13324 
                 13630 
                 13936 
               
               
                 class I 
               
               
                 PD1 
                 PD1-4H1-vL 
                 7913 
                 10674 
                 13325 
                 13631 
                 13937 
               
               
                 PD1 
                 PD1-5C4-vL 
                 7914 
                 10675 
                 13326 
                 13632 
                 13938 
               
               
                 PDL1 
                 PDL1-10A5-vL 
                 7915 
                 10676 
                 13327 
                 13633 
                 13939 
               
               
                 PDL1 
                 PDL1-Atezoli-vL 
                 7916 
                 10677 
                 13328 
                 13634 
                 13940 
               
               
                 PDL1 
                 PDL1-SP142-vL 
                 7917 
                 10678 
                 13329 
                 13635 
                 13941 
               
               
                 PR1/MHC class 
                 PR1-vL 
                 7918 
                 10679 
                 13330 
                 13636 
                 13942 
               
               
                 I 
               
               
                 PSCA 
                 PSCA-Ha14-117-vL 
                 7919 
                 10680 
                 13331 
                 13637 
                 13943 
               
               
                 PSCA 
                 PSCA-Ha14-121-vL 
                 7920 
                 10681 
                 13332 
                 13638 
                 13944 
               
               
                 PSMA 
                 PSMA-006-vL 
                 7921 
                 10682 
                 13333 
                 13639 
                 13945 
               
               
                 PSMA 
                 PSMA-J591-vL 
                 7922 
                 10683 
                 13334 
                 13640 
                 13946 
               
               
                 PTK7 
                 PTK7-hSC6-23-vL 
                 7923 
                 10684 
                 13335 
                 13641 
                 13947 
               
               
                 PTK7 
                 PTK7-SC6-10-2-vL 
                 7924 
                 10685 
                 13336 
                 13642 
                 13948 
               
               
                 ROR1 
                 ROR1-4A5-vL 
                 7925 
                 10686 
                 13337 
                 13643 
                 13949 
               
               
                 ROR1 
                 ROR1-4C10-vL 
                 7926 
                 10687 
                 13338 
                 13644 
                 13950 
               
               
                 SLea 
                 SLea-5B1-vL 
                 7927 
                 10688 
                 13339 
                 13645 
                 13951 
               
               
                 SLea 
                 SLea-7E3-vL 
                 7928 
                 10689 
                 13340 
                 13646 
                 13952 
               
               
                 SSEA4 
                 SSEA4-vL 
                 7929 
                 10690 
                 13341 
                 13647 
                 13953 
               
               
                 TCRB1 
                 TCRB1-E09-vL 
                 7930 
                 10691 
                 13342 
                 13648 
                 13954 
               
               
                 TCRB1 
                 TCRB1-Jovi1-vL 
                 7931 
                 10692 
                 13343 
                 13649 
                 13955 
               
               
                 TCRB2 
                 TCRB2-CP01-D05- 
                 7932 
                 10693 
                 13344 
                 13650 
                 13956 
               
               
                   
                 vL 
               
               
                 TCRB2 
                 TCRB2-CP01-E05- 
                 7933 
                 10694 
                 13345 
                 13651 
                 13957 
               
               
                   
                 vL 
               
               
                 TCRgd 
                 TCRgd-G5-4-vL 
                 7934 
                 10695 
                 13346 
                 13652 
                 13958 
               
               
                 TERT/MHC 
                 TERT-3G3-T865-vL 
                 7935 
                 10696 
                 13347 
                 13653 
                 13959 
               
               
                 class I 
               
               
                 TERT/MHC 
                 TERT-4A9-T540-vL 
                 7936 
                 10697 
                 13348 
                 13654 
                 13960 
               
               
                 class I 
               
               
                 TGFBR2 
                 TGFBR2-Ab1-vL 
                 7937 
                 10698 
                 13349 
                 13655 
                 13961 
               
               
                 TIM1 
                 TIM1-HVCR1-270- 
                 7938 
                 10699 
                 13350 
                 13656 
                 13962 
               
               
                   
                 2-vL 
               
               
                 TIM1 
                 Tim1HVCR1-ARD5- 
                 7939 
                 10700 
                 13351 
                 13657 
                 13963 
               
               
                   
                 vL 
               
               
                 TnAg 
                 TnAg-vL 
                 7940 
                 10701 
                 13352 
                 13658 
                 13964 
               
               
                 Tn-Muc1 
                 Tn-Muc1-hu5E5-vL 
                 7941 
                 10702 
                 13353 
                 13659 
                 13965 
               
               
                 TROP2 
                 TROP2-ARA47- 
                 7942 
                 10703 
                 13354 
                 13660 
                 13966 
               
               
                   
                 HV3KV3-vL 
               
               
                 TROP2 
                 TROP2-h7E6-SVG- 
                 7943 
                 10704 
                 13355 
                 13661 
                 13967 
               
               
                   
                 vL 
               
               
                 TSHR 
                 TSHR-5C9-vL 
                 7944 
                 10705 
                 13356 
                 13662 
                 13968 
               
               
                 TSHR 
                 TSHR-K1-70-vL 
                 7945 
                 10706 
                 13357 
                 13663 
                 13969 
               
               
                 TSHR 
                 TSHR-KB1-vL 
                 7946 
                 10707 
                 13358 
                 13664 
                 13970 
               
               
                 TSLRP 
                 TSLRP-vL 
                 7947 
                 10708 
                 13359 
                 13665 
                 13971 
               
               
                 Tyrosinase/MHC 
                 Tyro-B2-vL 
                 7948 
                 10709 
                 13360 
                 13666 
                 13972 
               
               
                 class I 
               
               
                 Tyrosinase/MHC 
                 Tyro-Mc1-vL 
                 7949 
                 10710 
                 13361 
                 13667 
                 13973 
               
               
                 class I 
               
               
                 Tyrosinase/MHC 
                 TA2-vL 
                 7950 
                 10711 
                 13362 
                 13668 
                 13974 
               
               
                 class I 
               
               
                 VEGFR3 
                 VEGFR3-Ab1-vL 
                 7951 
                 10712 
                 13363 
                 13669 
                 13975 
               
               
                 WT1/MHC class 
                 WT1-Ab13-vL 
                 7952 
                 10713 
                 13364 
                 13670 
                 13976 
               
               
                 I 
               
               
                 WT1/MHC class 
                 WT1-Ab15-vL 
                 7953 
                 10714 
                 13365 
                 13671 
                 13977 
               
               
                 I 
               
               
                 WT1/MHC class 
                 WT1-Ab1-vL 
                 7954 
                 10715 
                 13366 
                 13672 
                 13978 
               
               
                 I 
               
               
                 WT1/MHC class 
                 WT1-Ab5-vL 
                 7955 
                 10716 
                 13367 
                 13673 
                 13979 
               
               
                 I 
               
               
                 EBV-gp350 
                 EBV-gp350-vL 
                 7956 
                 10717 
                 13368 
                 13674 
                 13980 
               
               
                 CD123 
                 CD123-1172-vL 
                 7957 
                 10718 
                 13369 
                 13675 
                 13981 
               
               
                 CDH19 
                 CDH19-4B10-vL 
                 7958 
                 10719 
                 13370 
                 13676 
                 13982 
               
               
                 Folate Receptor 
                 FRbeta-m923-vL 
                 7959 
                 10720 
                 13371 
                 13677 
                 13983 
               
               
                 Beta 
               
               
                 LHR 
                 LHR-8B7-vL 
                 7960 
                 10721 
                 13372 
                 13678 
                 13984 
               
               
                 LHR 
                 LHR-5F4-21-vL 
                 7961 
                 10722 
                 13373 
                 13679 
                 13985 
               
               
                 B7H4 
                 B7H4-hu22C10-vL 
                 7962 
                 10723 
                 13374 
                 13680 
                 13986 
               
               
                 B7H4 
                 B7H4-hu1D11-vL 
                 7963 
                 10724 
                 13375 
                 13681 
                 13987 
               
               
                 IgE 
                 IgE-omalizumab-vL 
                 7964 
                 10725 
                 13376 
                 13682 
                 13988 
               
               
                 CD23 
                 CD23-p5E8-vL 
                 7965 
                 10726 
                 13377 
                 13683 
                 13989 
               
               
                 GCC 
                 GCC-5F9-vL 
                 7966 
                 10727 
                 13378 
                 13684 
                 13990 
               
               
                 GCC 
                 GCC-Ab229-vL 
                 7967 
                 10728 
                 13379 
                 13685 
                 13991 
               
               
                 CD200R 
                 CD200R-huDx182- 
                 7968 
                 10729 
                 13380 
                 13686 
                 13992 
               
               
                   
                 vL 
               
               
                 AFP/MHC class 
                 AFP-61-vL 
                 7969 
                 10730 
                 13381 
                 13687 
                 13993 
               
               
                 I 
               
               
                 AFP/MHC class 
                 AFP-76-vL 
                 7970 
                 10731 
                 13382 
                 13688 
                 13994 
               
               
                 I 
               
               
                 AFP/MHC class 
                 AFP-79-vL 
                 7971 
                 10732 
                 13383 
                 13689 
                 13995 
               
               
                 I 
               
               
                 BCMA 
                 BCMA-ET-03-vL 
                 7972 
                 10733 
                 13384 
                 13690 
                 13996 
               
               
                 BCMA 
                 BCMA- 
                 7973 
                 10734 
                 13385 
                 13691 
                 13997 
               
               
                   
                 huC11.D5.3L1H3-vL 
               
               
                 BCMA 
                 BCMA-huC13-F12- 
                 7974 
                 10735 
                 13386 
                 13692 
                 13998 
               
               
                   
                 vL 
               
               
                 CD123 
                 CD123-DART-1-vL 
                 7975 
                 10736 
                 13387 
                 13693 
                 13999 
               
               
                 CD123 
                 CD123-DART-2-vL 
                 7976 
                 10737 
                 13388 
                 13694 
                 14000 
               
               
                 CD123 
                 CD123-I3RB18-vL 
                 7977 
                 10738 
                 13389 
                 13695 
                 14001 
               
               
                 CD123 
                 CD123-hu3E3-vL 
                 7978 
                 10739 
                 13390 
                 13696 
                 14002 
               
               
                 CD123 
                 CD123-9F6-vL 
                 7979 
                 10740 
                 13391 
                 13697 
                 14003 
               
               
                 CD123 
                 CD123-I3RB2-vL 
                 7980 
                 10741 
                 13392 
                 13698 
                 14004 
               
               
                 CD123 
                 CD123-1176-vL 
                 7981 
                 10742 
                 13393 
                 13699 
                 14005 
               
               
                 CD123 
                 CD123-8B11-vL 
                 7982 
                 10743 
                 13394 
                 13700 
                 14006 
               
               
                 CD123 
                 CD123-2B8-vL 
                 7983 
                 10744 
                 13395 
                 13701 
                 14007 
               
               
                 CD123 
                 CD123-9D7-vL 
                 7984 
                 10745 
                 13396 
                 13702 
                 14008 
               
               
                 CD123 
                 CD123-3B10-vL 
                 7985 
                 10746 
                 13397 
                 13703 
                 14009 
               
               
                 CD19 
                 CD19-MEDI-3649- 
                 7986 
                 10747 
                 13398 
                 13704 
                 14010 
               
               
                   
                 vL 
               
               
                 CD19 
                 CD19-Medrex-24D1- 
                 7987 
                 10748 
                 13399 
                 13705 
                 14011 
               
               
                   
                 vL 
               
               
                 CD19 
                 CD19-MOR0028-vL 
                 7988 
                 10749 
                 13400 
                 13706 
                 14012 
               
               
                 CD19 
                 CD19-HD37-H2L1- 
                 7989 
                 10750 
                 13401 
                 13707 
                 14013 
               
               
                   
                 vL 
               
               
                 CD19 
                 CD19-huBly3-vL 
                 7990 
                 10751 
                 13402 
                 13708 
                 14014 
               
               
                 CD19 
                 CD19-huSJ25C1-vL 
                 7991 
                 10752 
                 13403 
                 13709 
                 14015 
               
               
                 CD19 
                 CD19-hB4-vL 
                 7992 
                 10753 
                 13404 
                 13710 
                 14016 
               
               
                 CD19 
                 CD19-hu-mROO5-1- 
                 7993 
                 10754 
                 13405 
                 13711 
                 14017 
               
               
                   
                 vL 
               
               
                 CD19 
                 CD19-hA19-vL 
                 7994 
                 10755 
                 13406 
                 13712 
                 14018 
               
               
                 CD20 
                 CD20-Leu16-vL 
                 7995 
                 10756 
                 13407 
                 13713 
                 14019 
               
               
                 CD20 
                 CD20-11B8-vL 
                 7996 
                 10757 
                 13408 
                 13714 
                 14020 
               
               
                 CD20 
                 CD20-2C6-vL 
                 7997 
                 10758 
                 13409 
                 13715 
                 14021 
               
               
                 CD20 
                 CD20-2H7-vL 
                 7998 
                 10759 
                 13410 
                 13716 
                 14022 
               
               
                 CD20 
                 CD20-hA20-vL 
                 7999 
                 10760 
                 13411 
                 13717 
                 14023 
               
               
                 CD20 
                 CD20-BM-CA-1925- 
                 8000 
                 10761 
                 13412 
                 13718 
                 14024 
               
               
                   
                 v4-vL 
               
               
                 CD20 
                 CD20-Ubli-v4-vL 
                 8001 
                 10762 
                 13413 
                 13719 
                 14025 
               
               
                 CD20 
                 CD20-h1F5-vL 
                 8002 
                 10763 
                 13414 
                 13720 
                 14026 
               
               
                 CD20 
                 CD20-7D8-vL 
                 8003 
                 10764 
                 13415 
                 13721 
                 14027 
               
               
                 CD20 
                 CD20-AME-33-vL 
                 8004 
                 10765 
                 13416 
                 13722 
                 14028 
               
               
                 CD33 
                 CD33- 
                 8005 
                 10766 
                 13417 
                 13723 
                 14029 
               
               
                   
                 Boehr2800308-vL 
               
               
                 CD33 
                 CD33-Him3-4-vL 
                 8006 
                 10767 
                 13418 
                 13724 
                 14030 
               
               
                 CD33 
                 CD33-SGNh2H12- 
                 8007 
                 10768 
                 13419 
                 13725 
                 14031 
               
               
                   
                 vL 
               
               
                 CD33 
                 CD33-15G15-33-vL 
                 8008 
                 10769 
                 13420 
                 13726 
                 14032 
               
               
                 CD33 
                 CD33-33H4-vL 
                 8009 
                 10770 
                 13421 
                 13727 
                 14033 
               
               
                 CD33 
                 CD33-9C3-2-vL 
                 8010 
                 10771 
                 13422 
                 13728 
                 14034 
               
               
                 CD99 
                 CD99-hu12E7-vL 
                 8011 
                 10772 
                 13423 
                 13729 
                 14035 
               
               
                 CLL1 
                 CLL1-21C9-L2H3- 
                 8012 
                 10773 
                 13424 
                 13730 
                 14036 
               
               
                   
                 vL 
               
               
                 CLL1 
                 CLL1-6E7L4H1e-vL 
                 8013 
                 10774 
                 13425 
                 13731 
                 14037 
               
               
                 CLL1 
                 CLL1-hu1075-v1-vL 
                 8014 
                 10775 
                 13426 
                 13732 
                 14038 
               
               
                 CLL1 
                 CLL1-hu1075-v2-vL 
                 8015 
                 10776 
                 13427 
                 13733 
                 14039 
               
               
                 CS1 
                 CS1-PDL241-vL 
                 8016 
                 10777 
                 13428 
                 13734 
                 14040 
               
               
                 CS1 
                 CS1-Hu27A-vL 
                 8017 
                 10778 
                 13429 
                 13735 
                 14041 
               
               
                 CS1 
                 CS1-ScHu34C3-vL 
                 8018 
                 10779 
                 13430 
                 13736 
                 14042 
               
               
                 CS1 
                 CS1-Hu31-D2-vL 
                 8019 
                 10780 
                 13431 
                 13737 
                 14043 
               
               
                 CS1 
                 CS1-Luc34-vL 
                 8020 
                 10781 
                 13432 
                 13738 
                 14044 
               
               
                 CS1 
                 CS1-LucX2-vL 
                 8021 
                 10782 
                 13433 
                 13739 
                 14045 
               
               
                 FITC 
                 FITC-4M-53-vL 
                 8022 
                 10783 
                 13434 
                 13740 
                 14046 
               
               
                 FITC 
                 FITC-E2-vL 
                 8023 
                 10784 
                 13435 
                 13741 
                 14047 
               
               
                 GPRC5D 
                 GPRC5D-ET150-1- 
                 8024 
                 10785 
                 13436 
                 13742 
                 14048 
               
               
                   
                 vL 
               
               
                 GPRC5D 
                 GPRC5D-ET150-2- 
                 8025 
                 10786 
                 13437 
                 13743 
                 14049 
               
               
                   
                 vL 
               
               
                 HLA-A2 
                 HLA-A2-3PB2-vL 
                 8026 
                 10787 
                 13438 
                 13744 
                 14050 
               
               
                 HPV16- 
                 HPV16-7-8-vL 
                 8027 
                 10788 
                 13439 
                 13745 
                 14051 
               
               
                 E7/MHC class I 
               
               
                 HPV16- 
                 HPV16-2-vL 
                 8028 
                 10789 
                 13440 
                 13746 
                 14052 
               
               
                 E7/MHC class I 
               
               
                 Tissue Factor 1 
                 TF1-98-vL 
                 8029 
                 10790 
                 13441 
                 13747 
                 14053 
               
               
                 (TF1) 
               
               
                 Tn-Muc1 
                 Tn-Muc1-5E5-vL 
                 8030 
                 10791 
                 13442 
                 13748 
                 14054 
               
               
                 Ig Kappa-Light 
                 Kappa-LC1-vL 
                 8031 
                 10792 
                 13443 
                 13749 
                 14055 
               
               
                 Chain 
               
               
                 PTK7 
                 PTK7-7C8-vL 
                 8032 
                 10793 
                 13444 
                 13750 
                 14056 
               
               
                 PTK7 
                 PTK7-12C6a-vL 
                 8033 
                 10794 
                 13445 
                 13751 
                 14057 
               
               
                 CD19 
                 hCD19-EUK5-13-vL 
                 8034 
                 10795 
                 13446 
                 13752 
                 14058 
               
               
                 Ras/MHC class I 
                 Ras-Ab2-vL 
                 8035 
                 10796 
                 13447 
                 13753 
                 14059 
               
               
                 Ras/MHC class I 
                 Ras-Ab4-vL 
                 8036 
                 10797 
                 13448 
                 13754 
                 14060 
               
               
                 CLD18A2 
                 CLD18A2-43A11-vL 
                 8037 
                 10798 
                 13449 
                 13755 
                 14061 
               
               
                 CLD18A2 
                 CLD18A2-175D10- 
                 8038 
                 10799 
                 13450 
                 13756 
                 14062 
               
               
                   
                 vL 
               
               
                 CD43 
                 CD43-huJL-1-257- 
                 8039 
                 10800 
                 13451 
                 13757 
                 14063 
               
               
                   
                 10-vL 
               
               
                 CD69L 
                 CD69L-DREG200- 
                 8040 
                 10801 
                 13452 
                 13758 
                 14064 
               
               
                   
                 vL 
               
               
                 NY-ESO 
                 NYESO-35-15-vL 
                 8041 
                 10802 
                 13453 
                 13759 
                 14065 
               
               
                 P-glycoprotein 
                 Pgp-9F11-vL 
                 8042 
                 10803 
                 13454 
                 13760 
                 14066 
               
               
                 (MDR1) 
               
               
                 Streptag 
                 Streptag-vL 
                 8043 
                 10804 
                 13455 
                 13761 
                 14067 
               
               
                 BCMA 
                 BCMA-huC13-F12- 
                 8044 
                 10805 
                 13456 
                 13762 
                 14068 
               
               
                   
                 L1H2-vL 
               
               
                 BCMA 
                 BCMA-huC12A3- 
                 8045 
                 10806 
                 13457 
                 13763 
                 14069 
               
               
                   
                 L3H3-vL 
               
               
                 MPL/TPO-R 
                 Hu-161-2-vL 
                 8046 
                 10807 
                 13458 
                 13764 
                 14070 
               
               
                 P-glycoprotein 
                 Pgp-MRK16-vL 
                 8047 
                 10808 
                 13459 
                 13765 
                 14071 
               
               
                 (MDR1) 
               
               
                 CD22 
                 CD22-5-vL 
                 8048 
                 10809 
                 13460 
                 13766 
                 14072 
               
               
                 CD22 
                 CD22-10-vL 
                 8049 
                 10810 
                 13461 
                 13767 
                 14073 
               
               
                 CD22 
                 CD22-31-vL 
                 8050 
                 10811 
                 13462 
                 13768 
                 14074 
               
               
                 CD22 
                 CD22-53-vL 
                 8051 
                 10812 
                 13463 
                 13769 
                 14075 
               
               
                 CD22 
                 CD22-65-vL 
                 8052 
                 10813 
                 13464 
                 13770 
                 14076 
               
               
                 CD19 
                 hu-FMC65-1-vL 
                 8053 
                 10814 
                 13465 
                 13771 
                 14077 
               
               
                 MPL/TPO-R 
                 MPL-hu-175-2-vL 
                 8054 
                 10815 
                 13466 
                 13772 
                 14078 
               
               
                 MPL/TPO-R 
                 MPL-hu-111-2-vL 
                 8055 
                 10816 
                 13467 
                 13773 
                 14079 
               
               
                 CD179a 
                 CD179a-2460-B04- 
                 8056 
                 10817 
                 13468 
                 13774 
                 14080 
               
               
                   
                 vL 
               
               
                 CD179a 
                 CD179a-2462-E07- 
                 8057 
                 10818 
                 13469 
                 13775 
                 14081 
               
               
                   
                 vL 
               
               
                 CD37 
                 CD37-TRU-HL-vL 
                 8058 
                 10819 
                 13470 
                 13776 
                 14082 
               
               
                 CD37 
                 huCD37-Boeh-vL 
                 8059 
                 10820 
                 13471 
                 13777 
                 14083 
               
               
                 CD70 
                 CD70-13D-vL 
                 8060 
                 10821 
                 13472 
                 13778 
                 14084 
               
               
                 CD70 
                 CD70-16D-vL 
                 8061 
                 10822 
                 13473 
                 13779 
                 14085 
               
               
                 CD70 
                 CD70-21D-vL 
                 8062 
                 10823 
                 13474 
                 13780 
                 14086 
               
               
                 CD70 
                 CD70-1G2D-vL 
                 8063 
                 10824 
                 13475 
                 13781 
                 14087 
               
               
                 CD70 
                 CD70-hu2H5-vL 
                 8064 
                 10825 
                 13476 
                 13782 
                 14088 
               
               
                 CD70 
                 CD70-69A7-vL 
                 8065 
                 10826 
                 13477 
                 13783 
                 14089 
               
               
                 CD70 
                 CD70-10B4-vL 
                 8066 
                 10827 
                 13478 
                 13784 
                 14090 
               
               
                 CD70 
                 CD70-24D-vL 
                 8067 
                 10828 
                 13479 
                 13785 
                 14091 
               
               
                 CD70 
                 CD70-25D-vL 
                 8068 
                 10829 
                 13480 
                 13786 
                 14092 
               
               
                 HIV1-envelop 
                 HIV1-N49P6-vL 
                 8069 
                 10830 
                 13481 
                 13787 
                 14093 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N49P7-vL 
                 8070 
                 10831 
                 13482 
                 13788 
                 14094 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N49P11-vL 
                 8071 
                 10832 
                 13483 
                 13789 
                 14095 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P1-1 
                 8072 
                 10833 
                 13484 
                 13790 
                 14096 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P25-vL 
                 8073 
                 10834 
                 13485 
                 13791 
                 14097 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N49P9-vL 
                 8074 
                 10835 
                 13486 
                 13792 
                 14098 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P2-1-vL 
                 8075 
                 10836 
                 13487 
                 13793 
                 14099 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P31-1-vL 
                 8076 
                 10837 
                 13488 
                 13794 
                 14100 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P22-vL 
                 8077 
                 10838 
                 13489 
                 13795 
                 14101 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P38-vL 
                 8078 
                 10839 
                 13490 
                 13796 
                 14102 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P30-vL 
                 8079 
                 10840 
                 13491 
                 13797 
                 14103 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P36-vL 
                 8080 
                 10841 
                 13492 
                 13798 
                 14104 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P39-vL 
                 8081 
                 10842 
                 13493 
                 13799 
                 14105 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N6039-1-vL 
                 8082 
                 10843 
                 13494 
                 13800 
                 14106 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P47-vL 
                 8083 
                 10844 
                 13495 
                 13801 
                 14107 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P48-vL 
                 8084 
                 10845 
                 13496 
                 13802 
                 14108 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P51-vL 
                 8085 
                 10846 
                 13497 
                 13803 
                 14109 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P35-vL 
                 8086 
                 10847 
                 13498 
                 13804 
                 14110 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-N60P37-vL 
                 8087 
                 10848 
                 13499 
                 13805 
                 14111 
               
               
                 glycoprotein 
               
               
                 Lym1 
                 Hu-Lym1-vL 
                 8088 
                 10849 
                 13500 
                 13806 
                 14112 
               
               
                 Lym2 
                 Hu-Lym2-vL 
                 8089 
                 10850 
                 13501 
                 13807 
                 14113 
               
               
                 BCMA 
                 BCMA-USC1-vL 
                 8090 
                 10851 
                 13502 
                 13808 
                 14114 
               
               
                 BCMA 
                 BCMA-USC2-vL 
                 8091 
                 10852 
                 13503 
                 13809 
                 14115 
               
               
                 BCMA 
                 BCMA-USC3-vL 
                 8092 
                 10853 
                 13504 
                 13810 
                 14116 
               
               
                 BCMA 
                 BCMA-USC4-vL 
                 8093 
                 10854 
                 13505 
                 13811 
                 14117 
               
               
                 BCMA 
                 BCMA-USC5-vL 
                 8094 
                 10855 
                 13506 
                 13812 
                 14118 
               
               
                 BCMA 
                 BCMA-USC6-vL 
                 8095 
                 10856 
                 13507 
                 13813 
                 14119 
               
               
                 BCMA 
                 BCMA-USC7-vL 
                 8096 
                 10857 
                 13508 
                 13814 
                 14120 
               
               
                 CD43 
                 CD43-huJL-1-257- 
                 8097 
                 10858 
                 13509 
                 13815 
                 14121 
               
               
                   
                 10-vL 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6B 
               
             
            
               
                   
               
               
                 TARGET ANTIGENS, NAMES AND SEQ IDS OF 
               
               
                 vH FRAGMENTS AND SEQ IDs of CDR1-3 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 SEQ 
                 SEQ 
                 SEQ 
                 SEQ 
                 SEQ 
               
               
                   
                   
                 ID vH 
                 ID vH 
                 ID-vH 
                 ID-vH 
                 ID-vH 
               
               
                 TARGET 
                 NAME of vH 
                 (DNA) 
                 (PRT) 
                 CDR1 
                 CDR2 
                 CDR3 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 ALK 
                 Alk-48-vH 
                 8098 
                 10859 
                 14122 
                 14428 
                 14734 
               
               
                 ALK 
                 Alk-58-vH 
                 8099 
                 10860 
                 14123 
                 14429 
                 14735 
               
               
                 Amyloid 
                 Amyloid-158-vH 
                 8100 
                 10861 
                 14124 
                 14430 
                 14736 
               
               
                 BCMA 
                 BCMA-ET-40-vH 
                 8101 
                 10862 
                 14125 
                 14431 
                 14737 
               
               
                 BCMA 
                 BCMA-ET-54-vH 
                 8102 
                 10863 
                 14126 
                 14432 
                 14738 
               
               
                 BCMA 
                 BCMA-huC12A3-vH 
                 8103 
                 10864 
                 14127 
                 14433 
                 14739 
               
               
                 BCMA 
                 BCMA-J6M0-vH 
                 8104 
                 10865 
                 14128 
                 14434 
                 14740 
               
               
                 CCR4 
                 CCR4-humAb1567- 
                 8105 
                 10866 
                 14129 
                 14435 
                 14741 
               
               
                   
                 vH 
               
               
                 CD123 
                 CD123-CSL362-vH 
                 8106 
                 10867 
                 14130 
                 14436 
                 14742 
               
               
                 CD138 
                 CD138-vH 
                 8107 
                 10868 
                 14131 
                 14437 
                 14743 
               
               
                 CD179b 
                 CD179b-vH 
                 8108 
                 10869 
                 14132 
                 14438 
                 14744 
               
               
                 CD19 
                 CD19-4G7-vH 
                 8109 
                 10870 
                 14133 
                 14439 
                 14745 
               
               
                 CD19 
                 CD19Bu12-vH 
                 8110 
                 10871 
                 14134 
                 14440 
                 14746 
               
               
                 CD19 
                 CD19Bu12-[2]-vH 
                 8111 
                 10872 
                 14135 
                 14441 
                 14747 
               
               
                 CD19 
                 CD19MM-vH 
                 8112 
                 10873 
                 14136 
                 14442 
                 14748 
               
               
                 CD19 
                 FMC63-vH 
                 8113 
                 10874 
                 14137 
                 14443 
                 14749 
               
               
                 CD19 
                 FMC-63-vH 
                 8114 
                 10875 
                 14138 
                 14444 
                 14750 
               
               
                 CD19 
                 huFMC63-11-vH 
                 8115 
                 10876 
                 14139 
                 14445 
                 14751 
               
               
                 CD20 
                 CD20-2F2-vH 
                 8116 
                 10877 
                 14140 
                 14446 
                 14752 
               
               
                 CD20 
                 CD20-GA101-vH 
                 8117 
                 10878 
                 14141 
                 14447 
                 14753 
               
               
                 CD22 
                 CD22-h10F4-vH 
                 8118 
                 10879 
                 14142 
                 14448 
                 14754 
               
               
                 CD22 
                 CD22- 
                 8119 
                 10880 
                 14143 
                 14449 
                 14755 
               
               
                   
                 H22Rhov2ACDRKA-vH 
               
               
                 CD22 
                 CD22m971-vH 
                 8120 
                 10881 
                 14144 
                 14450 
                 14756 
               
               
                 CD276 
                 CD276-17-vH 
                 8121 
                 10882 
                 14145 
                 14451 
                 14757 
               
               
                 CD30 
                 CD30-5F11-vH 
                 8122 
                 10883 
                 14146 
                 14452 
                 14758 
               
               
                 CD30 
                 CD30-Ac10-vH 
                 8123 
                 10884 
                 14147 
                 14453 
                 14759 
               
               
                 CD32 
                 CD32-Med9-vH 
                 8124 
                 10885 
                 14148 
                 14454 
                 14760 
               
               
                 CD324 
                 CD324-hSC10-17-vH 
                 8125 
                 10886 
                 14149 
                 14455 
                 14761 
               
               
                 CD324 
                 CD324-SC10-6-vH 
                 8126 
                 10887 
                 14150 
                 14456 
                 14762 
               
               
                 CD33 
                 CD33-huMyc9-vH 
                 8127 
                 10888 
                 14151 
                 14457 
                 14763 
               
               
                 CD33 
                 CD33-AF5-vH 
                 8128 
                 10889 
                 14152 
                 14458 
                 14764 
               
               
                 CD34 
                 CD34-hu4C7-vH 
                 8129 
                 10890 
                 14153 
                 14459 
                 14765 
               
               
                 CD44v6 
                 CD44v6-Biwa8-vH 
                 8130 
                 10891 
                 14154 
                 14460 
                 14766 
               
               
                 CD5 
                 CD5-18-vH 
                 8131 
                 10892 
                 14155 
                 14461 
                 14767 
               
               
                 CD5 
                 CD5-9-vH 
                 8132 
                 10893 
                 14156 
                 14462 
                 14768 
               
               
                 CD70 
                 CD70-h1F6-vH 
                 8133 
                 10894 
                 14157 
                 14463 
                 14769 
               
               
                 CD79b 
                 CD79b-2F2-vH 
                 8134 
                 10895 
                 14158 
                 14464 
                 14770 
               
               
                 CD79b 
                 huMA79bv28-vH 
                 8135 
                 10896 
                 14159 
                 14465 
                 14771 
               
               
                 CDH17 
                 CDH17-PTA001A4- 
                 8136 
                 10897 
                 14160 
                 14466 
                 14772 
               
               
                   
                 vH 
               
               
                 CDH19 
                 CDH19-16A4-vH 
                 8137 
                 10898 
                 14161 
                 14467 
                 14773 
               
               
                 CDH6 
                 CDH6-NOV710-vH 
                 8138 
                 10899 
                 14162 
                 14468 
                 14774 
               
               
                 CDH6 
                 CDH6-NOV712-vH 
                 8139 
                 10900 
                 14163 
                 14469 
                 14775 
               
               
                 CLEC5A 
                 CLEC5A-3E12A2- 
                 8140 
                 10901 
                 14164 
                 14470 
                 14776 
               
               
                   
                 vH 
               
               
                 CLEC5A 
                 CLEC5A-8H8F5-vH 
                 8141 
                 10902 
                 14165 
                 14471 
                 14777 
               
               
                 CLL1 
                 CLL1-M26-vH 
                 8142 
                 10903 
                 14166 
                 14472 
                 14778 
               
               
                 CLL1 
                 CLL1-M32-vH 
                 8143 
                 10904 
                 14167 
                 14473 
                 14779 
               
               
                 CMVpp65/MHC 
                 CMVpp65-F5-vH 
                 8144 
                 10905 
                 14168 
                 14474 
                 14780 
               
               
                 class I 
               
               
                 CS1 
                 huLuc63-vH 
                 8145 
                 10906 
                 14169 
                 14475 
                 14781 
               
               
                 CS1 
                 HuLuc64-vH 
                 8146 
                 10907 
                 14170 
                 14476 
                 14782 
               
               
                 CS1 
                 huLuc90-vH 
                 8147 
                 10908 
                 14171 
                 14477 
                 14783 
               
               
                 CSF2RA 
                 CSF2RA-Ab1-vH 
                 8148 
                 10909 
                 14172 
                 14478 
                 14784 
               
               
                 CSF2RA 
                 CSF2RA-Ab6-vH 
                 8149 
                 10910 
                 14173 
                 14479 
                 14785 
               
               
                 DLL3 
                 DLL3-hSC16-13-vH 
                 8150 
                 10911 
                 14174 
                 14480 
                 14786 
               
               
                 DLL3 
                 DLL3-hSC16-56-vH 
                 8151 
                 10912 
                 14175 
                 14481 
                 14787 
               
               
                 EBNA3c/MHC 
                 EBNA3c-315-vH 
                 8152 
                 10913 
                 14176 
                 14482 
                 14788 
               
               
                 class I 
               
               
                 EGFR 
                 Cetuximab-vH 
                 8153 
                 10914 
                 14177 
                 14483 
                 14789 
               
               
                 EGFR 
                 Nimotuzumab-vH 
                 8154 
                 10915 
                 14178 
                 14484 
                 14790 
               
               
                 EGFRviii 
                 EGFRviii-139-vH 
                 8155 
                 10916 
                 14179 
                 14485 
                 14791 
               
               
                 EGFRviii 
                 EGFRviii-2173-vH 
                 8156 
                 10917 
                 14180 
                 14486 
                 14792 
               
               
                 EpCam1 
                 EpCam1-D5K5-vH 
                 8157 
                 10918 
                 14181 
                 14487 
                 14793 
               
               
                 EpCam1 
                 Epcam1-MM1-vH 
                 8158 
                 10919 
                 14182 
                 14488 
                 14794 
               
               
                 FITC 
                 FITC-vH 
                 8159 
                 10920 
                 14183 
                 14489 
                 14795 
               
               
                 FLT3 
                 FLT3-NC7-vH 
                 8160 
                 10921 
                 14184 
                 14490 
                 14796 
               
               
                 HIV1-envelop 
                 HIV1-N6-vH 
                 8161 
                 10922 
                 14185 
                 14491 
                 14797 
               
               
                 glycoprotein 
               
               
                 Folate Receptor 
                 FRl-huMov19-vH 
                 8162 
                 10923 
                 14186 
                 14492 
                 14798 
               
               
                 1 (FR1) 
               
               
                 GAD 
                 GAD-G3H8-vH 
                 8163 
                 10924 
                 14187 
                 14493 
                 14799 
               
               
                 GD2 
                 GD2-hu14-18-vH 
                 8164 
                 10925 
                 14188 
                 14494 
                 14800 
               
               
                 GD2 
                 GD2-hu3F8-vH 
                 8165 
                 10926 
                 14189 
                 14495 
                 14801 
               
               
                 GD3 
                 GD3-KM-641-vH 
                 8166 
                 10927 
                 14190 
                 14496 
                 14802 
               
               
                 GFRa4 
                 GFRa4-P4-10-vH 
                 8167 
                 10928 
                 14191 
                 14497 
                 14803 
               
               
                 GFRa4 
                 GFRAlpha4-P4-6-vH 
                 8168 
                 10929 
                 14192 
                 14498 
                 14804 
               
               
                 GM1 
                 GM1-5B2-vH 
                 8169 
                 10930 
                 14193 
                 14499 
                 14805 
               
               
                 GM1 
                 GM1-7E5-vH 
                 8170 
                 10931 
                 14194 
                 14500 
                 14806 
               
               
                 gp100/MHC 
                 gp100-G2D12-vH 
                 8171 
                 10932 
                 14195 
                 14501 
                 14807 
               
               
                 class I 
               
               
                 gp100/MHC 
                 gp100-vH 
                 8172 
                 10933 
                 14196 
                 14502 
                 14808 
               
               
                 class I 
               
               
                 GPC3 
                 GPC3-4E5-vH 
                 8173 
                 10934 
                 14197 
                 14503 
                 14809 
               
               
                 gpNMB 
                 gpNMB-115-vH 
                 8174 
                 10935 
                 14198 
                 14504 
                 14810 
               
               
                 GPRC5D 
                 GPRC5D-ET150-18- 
                 8175 
                 10936 
                 14199 
                 14505 
                 14811 
               
               
                   
                 vH 
               
               
                 GPRC5D 
                 GPRC5D-ET150-5- 
                 8176 
                 10937 
                 14200 
                 14506 
                 14812 
               
               
                   
                 vH 
               
               
                 Her2 
                 Her2-Hu4D5-vH 
                 8177 
                 10938 
                 14201 
                 14507 
                 14813 
               
               
                 HIV1-gag (77- 
                 HIV1-E5-vH 
                 8178 
                 10939 
                 14202 
                 14508 
                 14814 
               
               
                 85)/MHC 
               
               
                 HIV1-envelop 
                 HIV1-3BNC117-vH 
                 8179 
                 10940 
                 14203 
                 14509 
                 14815 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-PGT-128-vH 
                 8180 
                 10941 
                 14204 
                 14510 
                 14816 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-VR-C01-vH 
                 8181 
                 10942 
                 14205 
                 14511 
                 14817 
               
               
                 glycoprotein 
               
               
                 HIV1-envelop 
                 HIV1-X5-vH 
                 8182 
                 10943 
                 14206 
                 14512 
                 14818 
               
               
                 glycoprotein 
               
               
                 HMW-MAA 
                 HMW-MAA-hIND- 
                 8183 
                 10944 
                 14207 
                 14513 
                 14819 
               
               
                   
                 vH 
               
               
                 HTLV1- 
                 TAX-T3E3-vH 
                 8184 
                 10945 
                 14208 
                 14514 
                 14820 
               
               
                 TAX/MHC class 
               
               
                 I 
               
               
                 HTLV1- 
                 TAX-T3F2-vH 
                 8185 
                 10946 
                 14209 
                 14515 
                 14821 
               
               
                 TAX/MHC class 
               
               
                 I 
               
               
                 IL11Ra 
                 IL11Ra-8E2-vH 
                 8186 
                 10947 
                 14210 
                 14516 
                 14822 
               
               
                 IL13Ra2 
                 IL13Ra2-hu107-vH 
                 8187 
                 10948 
                 14211 
                 14517 
                 14823 
               
               
                 IL13Ra2 
                 IL13Ra2-Hu108-vH 
                 8188 
                 10949 
                 14212 
                 14518 
                 14824 
               
               
                 IL6R 
                 IL6R-M83-vH 
                 8189 
                 10950 
                 14213 
                 14519 
                 14825 
               
               
                 Influenza A HA 
                 FLU-MEDI-8852-vH 
                 8190 
                 10951 
                 14214 
                 14520 
                 14826 
               
               
                 KSHV-gH 
                 YC15-vH 
                 8191 
                 10952 
                 14215 
                 14521 
                 14827 
               
               
                 KSHV-K8.1 
                 4C3-vH 
                 8192 
                 10953 
                 14216 
                 14522 
                 14828 
               
               
                 L1CAM 
                 L1CAM-9-3-HU3- 
                 8193 
                 10954 
                 14217 
                 14523 
                 14829 
               
               
                   
                 vH 
               
               
                 LAMP1 
                 LAMP1-humab1-2- 
                 8194 
                 10955 
                 14218 
                 14524 
                 14830 
               
               
                   
                 vH 
               
               
                 LAMP1 
                 LAMP1-Mb4-vH 
                 8195 
                 10956 
                 14219 
                 14525 
                 14831 
               
               
                 LewisY 
                 LewisY-huS193-vH 
                 8196 
                 10957 
                 14220 
                 14526 
                 14832 
               
               
                 Lym1 
                 Lym1-vH 
                 8197 
                 10958 
                 14221 
                 14527 
                 14833 
               
               
                 Lym2 
                 Lym2-vH 
                 8198 
                 10959 
                 14222 
                 14528 
                 14834 
               
               
                 MART1/MHC 
                 MART1-CAG10-vH 
                 8199 
                 10960 
                 14223 
                 14529 
                 14835 
               
               
                 class I 
               
               
                 MART1/MHC 
                 MART1-CLA12-vH 
                 8200 
                 10961 
                 14224 
                 14530 
                 14836 
               
               
                 class I 
               
               
                 Mesothelin 
                 Mesothelin-m912- 
                 8201 
                 10962 
                 14225 
                 14531 
                 14837 
               
               
                   
                 [2]-vH 
               
               
                 Mesothelin 
                 Mesothelin-m912-vH 
                 8202 
                 10963 
                 14226 
                 14532 
                 14838 
               
               
                 MPL (TPO-R) 
                 MPL-111-vH 
                 8203 
                 10964 
                 14227 
                 14533 
                 14839 
               
               
                 MPL (TPO-R) 
                 MPL-161-HL-vH 
                 8204 
                 10965 
                 14228 
                 14534 
                 14840 
               
               
                 MPL (TPO-R) 
                 MPL-161-vH 
                 8205 
                 10966 
                 14229 
                 14535 
                 14841 
               
               
                 MPL (TPO-R) 
                 MPL-175-vH 
                 8206 
                 10967 
                 14230 
                 14536 
                 14842 
               
               
                 MPL (TPO-R) 
                 MPL-178-vH 
                 8207 
                 10968 
                 14231 
                 14537 
                 14843 
               
               
                 MPL (TPO-R) 
                 MPL-huVB22Bw5- 
                 8208 
                 10969 
                 14232 
                 14538 
                 14844 
               
               
                   
                 vH 
               
               
                 MPL (TPO-R) 
                 MPL-12E10-vH 
                 8209 
                 10970 
                 14233 
                 14539 
                 14845 
               
               
                 MPL (TPO-R) 
                 MPL-AB317-vH 
                 8210 
                 10971 
                 14234 
                 14540 
                 14846 
               
               
                 Muc1/MHC 
                 MUC1-D6-M3A1-vH 
                 8211 
                 10972 
                 14235 
                 14541 
                 14847 
               
               
                 class I 
               
               
                 Muc1/MHC 
                 Muc1-D6-M3B8-vH 
                 8212 
                 10973 
                 14236 
                 14542 
                 14848 
               
               
                 class I 
               
               
                 Muc16 
                 Muc16-4H11-vH 
                 8213 
                 10974 
                 14237 
                 14543 
                 14849 
               
               
                 NKG2D 
                 NKG2D-MS-vH 
                 8214 
                 10975 
                 14238 
                 14544 
                 14850 
               
               
                 NYBR1 
                 NYBR1-vH 
                 8215 
                 10976 
                 14239 
                 14545 
                 14851 
               
               
                 NY-ESO/MHC 
                 NY-ESO-T1-vH 
                 8216 
                 10977 
                 14240 
                 14546 
                 14852 
               
               
                 class I 
               
               
                 NY-ESO/MHC 
                 NY-ESO-T2-vH 
                 8217 
                 10978 
                 14241 
                 14547 
                 14853 
               
               
                 class I 
               
               
                 PD1 
                 PD1-4H1-vH 
                 8218 
                 10979 
                 14242 
                 14548 
                 14854 
               
               
                 PD1 
                 PD1-5C4-vH 
                 8219 
                 10980 
                 14243 
                 14549 
                 14855 
               
               
                 PDL1 
                 PDL1-Atezoli-vH 
                 8220 
                 10981 
                 14244 
                 14550 
                 14856 
               
               
                 PDL1 
                 PDL1-SP142-vH 
                 8221 
                 10982 
                 14245 
                 14551 
                 14857 
               
               
                 PR1/MHC class 
                 PR1-vH 
                 8222 
                 10983 
                 14246 
                 14552 
                 14858 
               
               
                 I 
               
               
                 PSCA 
                 PSCA-Ha14-117-vH 
                 8223 
                 10984 
                 14247 
                 14553 
                 14859 
               
               
                 PSCA 
                 PSCA-Ha14-121-vH 
                 8224 
                 10985 
                 14248 
                 14554 
                 14860 
               
               
                 PSMA 
                 PSMA-006-vH 
                 8225 
                 10986 
                 14249 
                 14555 
                 14861 
               
               
                 PSMA 
                 PSMA-J591-vH 
                 8226 
                 10987 
                 14250 
                 14556 
                 14862 
               
               
                 PTK7 
                 PTK7-hSC6-23-vH 
                 8227 
                 10988 
                 14251 
                 14557 
                 14863 
               
               
                 PTK7 
                 PTK7-SC6-10-2-vH 
                 8228 
                 10989 
                 14252 
                 14558 
                 14864 
               
               
                 ROR1 
                 ROR1-4A5-vH 
                 8229 
                 10990 
                 14253 
                 14559 
                 14865 
               
               
                 ROR1 
                 ROR1-4C10-vH 
                 8230 
                 10991 
                 14254 
                 14560 
                 14866 
               
               
                 SLea 
                 SLea-5B1-vH 
                 8231 
                 10992 
                 14255 
                 14561 
                 14867 
               
               
                 SLea 
                 SLea-7E3-vH 
                 8232 
                 10993 
                 14256 
                 14562 
                 14868 
               
               
                 SSEA4 
                 SSEA4-vH 
                 8233 
                 10994 
                 14257 
                 14563 
                 14869 
               
               
                 TCRB1 
                 TCRB1-E09-vH 
                 8234 
                 10995 
                 14258 
                 14564 
                 14870 
               
               
                 TCRB1 
                 TCRB1-Jovi1-vH 
                 8235 
                 10996 
                 14259 
                 14565 
                 14871 
               
               
                 TCRB2 
                 TCRB2-CP01-D05- 
                 8236 
                 10997 
                 14260 
                 14566 
                 14872 
               
               
                   
                 vH 
               
               
                 TCRB2 
                 TCRB2-CP01-E05- 
                 8237 
                 10998 
                 14261 
                 14567 
                 14873 
               
               
                   
                 vH 
               
               
                 TCRgd 
                 TCRgd-G5-4-vH 
                 8238 
                 10999 
                 14262 
                 14568 
                 14874 
               
               
                 TERT/MHC 
                 TERT-3G3-T865-vH 
                 8239 
                 11000 
                 14263 
                 14569 
                 14875 
               
               
                 class I 
               
               
                 TERT/MHC 
                 TERT-4A9-T540-vH 
                 8240 
                 11001 
                 14264 
                 14570 
                 14876 
               
               
                 class I 
               
               
                 TGFBR2 
                 TGFBR2-Ab1-vH 
                 8241 
                 11002 
                 14265 
                 14571 
                 14877 
               
               
                 TIM1 
                 TIM1-HVCR1-270- 
                 8242 
                 11003 
                 14266 
                 14572 
                 14878 
               
               
                   
                 2-vH 
               
               
                 TIM1 
                 Tim1HVCR1-ARD5- 
                 8243 
                 11004 
                 14267 
                 14573 
                 14879 
               
               
                   
                 vH 
               
               
                 TnAg 
                 TnAg-vH 
                 8244 
                 11005 
                 14268 
                 14574 
                 14880 
               
               
                 Tn-Muc1 
                 Tn-Muc1-hu5E5-vH 
                 8245 
                 11006 
                 14269 
                 14575 
                 14881 
               
               
                 TROP2 
                 TROP2-ARA47- 
                 8246 
                 11007 
                 14270 
                 14576 
                 14882 
               
               
                   
                 HV3KV3-vH 
               
               
                 TROP2 
                 TROP2-h7E6-SVG- 
                 8247 
                 11008 
                 14271 
                 14577 
                 14883 
               
               
                   
                 vH 
               
               
                 TSHR 
                 TSHR-5C9-vH 
                 8248 
                 11009 
                 14272 
                 14578 
                 14884 
               
               
                 TSHR 
                 TSHR-K1-70-vH 
                 8249 
                 11010 
                 14273 
                 14579 
                 14885 
               
               
                 TSHR 
                 TSHR-KB1-vH 
                 8250 
                 11011 
                 14274 
                 14580 
                 14886 
               
               
                 TSLRP 
                 TSLRP-vH 
                 8251 
                 11012 
                 14275 
                 14581 
                 14887 
               
               
                 Tyrosinase/MHC 
                 Tyro-B2-vH 
                 8252 
                 11013 
                 14276 
                 14582 
                 14888 
               
               
                 class I 
               
               
                 Tyrosinase/MHC 
                 Tyro-Mc1-vH 
                 8253 
                 11014 
                 14277 
                 14583 
                 14889 
               
               
                 class I 
               
               
                 Tyrosinase/MHC 
                 TA2-vH 
                 8254 
                 11015 
                 14278 
                 14584 
                 14890 
               
               
                 class I 
               
               
                 VEGFR3 
                 VEGFR3-Ab1-vH 
                 8255 
                 11016 
                 14279 
                 14585 
                 14891 
               
               
                 WT1/MHC class 
                 WT1-Ab13-vH 
                 8256 
                 11017 
                 14280 
                 14586 
                 14892 
               
               
                 I 
               
               
                 WT1/MHC class 
                 WT1-Ab15-vH 
                 8257 
                 11018 
                 14281 
                 14587 
                 14893 
               
               
                 I 
               
               
                 WT1/MHC class 
                 WT1-Ab1-vH 
                 8258 
                 11019 
                 14282 
                 14588 
                 14894 
               
               
                 I 
               
               
                 WT1/MHC class 
                 WT1-Ab5-[2]-vH 
                 8259 
                 11020 
                 14283 
                 14589 
                 14895 
               
               
                 I 
               
               
                 WT1/MHC class 
                 WT1-Ab5-vH 
                 8260 
                 11021 
                 14284 
                 14590 
                 14896 
               
               
                 I 
               
               
                 EBV-gp350 
                 EBV-gp350-vH 
                 8261 
                 11022 
                 14285 
                 14591 
                 14897 
               
               
                 CD123 
                 CD123-1172-vH 
                 8262 
                 11023 
                 14286 
                 14592 
                 14898 
               
               
                 CDH19 
                 CDH19-4B10-vH 
                 8263 
                 11024 
                 14287 
                 14593 
                 14899 
               
               
                 Folate Receptor 
                 FRbeta-m923-vH 
                 8264 
                 11025 
                 14288 
                 14594 
                 14900 
               
               
                 Beta 
               
               
                 LHR 
                 LHR-8B7-vH 
                 8265 
                 11026 
                 14289 
                 14595 
                 14901 
               
               
                 LHR 
                 LHR-5F4-21-vH 
                 8266 
                 11027 
                 14290 
                 14596 
                 14902 
               
               
                 B7H4 
                 B7H4-hu22C10-vH 
                 8267 
                 11028 
                 14291 
                 14597 
                 14903 
               
               
                 B7H4 
                 B7H4-hu1D11-vH 
                 8268 
                 11029 
                 14292 
                 14598 
                 14904 
               
               
                 IgE 
                 IgE-omalizumab-vH 
                 8269 
                 11030 
                 14293 
                 14599 
                 14905 
               
               
                 CD23 
                 CD23-p5E8-vH 
                 8270 
                 11031 
                 14294 
                 14600 
                 14906 
               
               
                 GCC 
                 GCC-5F9-vH 
                 8271 
                 11032 
                 14295 
                 14601 
                 14907 
               
               
                 GCC 
                 GCC-Ab229-vH 
                 8272 
                 11033 
                 14296 
                 14602 
                 14908 
               
               
                 CD200R 
                 CD200R-huDx182- 
                 8273 
                 11034 
                 14297 
                 14603 
                 14909 
               
               
                   
                 vH 
               
               
                 AFP/MHC class 
                 AFP-61-vH 
                 8274 
                 11035 
                 14298 
                 14604 
                 14910 
               
               
                 I 
               
               
                 AFP/MHC class 
                 AFP-76-vH 
                 8275 
                 11036 
                 14299 
                 14605 
                 14911 
               
               
                 I 
               
               
                 AFP/MHC class 
                 AFP-79-vH 
                 8276 
                 11037 
                 14300 
                 14606 
                 14912 
               
               
                 I 
               
               
                 BCMA 
                 BCMA-ET-03-vH 
                 8277 
                 11038 
                 14301 
                 14607 
                 14913 
               
               
                 BCMA 
                 BCMA- 
                 8278 
                 11039 
                 14302 
                 14608 
                 14914 
               
               
                   
                 huC11.D5.3L1H3-vH 
               
               
                 BCMA 
                 BCMA-huC13-F12- 
                 8279 
                 11040 
                 14303 
                 14609 
                 14915 
               
               
                   
                 vH 
               
               
                 CD123 
                 CD123-DART-1-vH 
                 8280 
                 11041 
                 14304 
                 14610 
                 14916 
               
               
                 CD123 
                 CD123-DART-2-vH 
                 8281 
                 11042 
                 14305 
                 14611 
                 14917 
               
               
                 CD123 
                 CD123-13RB18-vH 
                 8282 
                 11043 
                 14306 
                 14612 
                 14918 
               
               
                 CD123 
                 CD123-hu3E3-vH 
                 8283 
                 11044 
                 14307 
                 14613 
                 14919 
               
               
                 CD123 
                 CD123-9F6-vH 
                 8284 
                 11045 
                 14308 
                 14614 
                 14920 
               
               
                 CD123 
                 CD123-I3RB2-vH 
                 8285 
                 11046 
                 14309 
                 14615 
                 14921 
               
               
                 CD123 
                 CD123-1176-vH 
                 8286 
                 11047 
                 14310 
                 14616 
                 14922 
               
               
                 CD123 
                 CD123-8B11-vH 
                 8287 
                 11048 
                 14311 
                 14617 
                 14923 
               
               
                 CD123 
                 CD123-2B8-vH 
                 8288 
                 11049 
                 14312 
                 14618 
                 14924 
               
               
                 CD123 
                 CD123-9D7-vH 
                 8289 
                 11050 
                 14313 
                 14619 
                 14925 
               
               
                 CD123 
                 CD123-3B10-vH 
                 8290 
                 11051 
                 14314 
                 14620 
                 14926 
               
               
                 CD19 
                 CD19-MEDI-3649- 
                 8291 
                 11052 
                 14315 
                 14621 
                 14927 
               
               
                   
                 vH 
               
               
                 CD19 
                 CD19-Medrex-24D1- 
                 8292 
                 11053 
                 14316 
                 14622 
                 14928 
               
               
                   
                 vH 
               
               
                 CD19 
                 CD19-MOR0028-vH 
                 8293 
                 11054 
                 14317 
                 14623 
                 14929 
               
               
                 CD19 
                 CD19-HD37-H2L1- 
                 8294 
                 11055 
                 14318 
                 14624 
                 14930 
               
               
                   
                 vH 
               
               
                 CD19 
                 CD19-huBly3-vH 
                 8295 
                 11056 
                 14319 
                 14625 
                 14931 
               
               
                 CD19 
                 CD19-huSJ25C1-vH 
                 8296 
                 11057 
                 14320 
                 14626 
                 14932 
               
               
                 CD19 
                 CD19-hB4-vH 
                 8297 
                 11058 
                 14321 
                 14627 
                 14933 
               
               
                 CD19 
                 CD19-hu-mROO5-1- 
                 8298 
                 11059 
                 14322 
                 14628 
                 14934 
               
               
                   
                 vH 
               
               
                 CD19 
                 CD19-hA19-vH 
                 8299 
                 11060 
                 14323 
                 14629 
                 14935 
               
               
                 CD20 
                 CD20-Leu16-vH 
                 8300 
                 11061 
                 14324 
                 14630 
                 14936 
               
               
                 CD20 
                 CD20-11B8-vH 
                 8301 
                 11062 
                 14325 
                 14631 
                 14937 
               
               
                 CD20 
                 CD20-2C6-vH 
                 8302 
                 11063 
                 14326 
                 14632 
                 14938 
               
               
                 CD20 
                 CD20-2H7-vH 
                 8303 
                 11064 
                 14327 
                 14633 
                 14939 
               
               
                 CD20 
                 CD20-hA20-vH 
                 8304 
                 11065 
                 14328 
                 14634 
                 14940 
               
               
                 CD20 
                 CD20-BM-CA-1925- 
                 8305 
                 11066 
                 14329 
                 14635 
                 14941 
               
               
                   
                 v4-vH 
               
               
                 CD20 
                 CD20-Ubli-v4-vH 
                 8306 
                 11067 
                 14330 
                 14636 
                 14942 
               
               
                 CD20 
                 CD20-h1F5-vH 
                 8307 
                 11068 
                 14331 
                 14637 
                 14943 
               
               
                 CD20 
                 CD20-7D8-vH 
                 8308 
                 11069 
                 14332 
                 14638 
                 14944 
               
               
                 CD20 
                 CD20-AME-33-vH 
                 8309 
                 11070 
                 14333 
                 14639 
                 14945 
               
               
                 CD33 
                 CD33- 
                 8310 
                 11071 
                 14334 
                 14640 
                 14946 
               
               
                   
                 Boehr2800308-vH 
               
               
                 CD33 
                 CD33-Him3-4-vH 
                 8311 
                 11072 
                 14335 
                 14641 
                 14947 
               
               
                 CD33 
                 CD33-SGNh2H12- 
                 8312 
                 11073 
                 14336 
                 14642 
                 14948 
               
               
                   
                 vH 
               
               
                 CD33 
                 CD33-15G15-33-vH 
                 8313 
                 11074 
                 14337 
                 14643 
                 14949 
               
               
                 CD33 
                 CD33-33H4-vH 
                 8314 
                 11075 
                 14338 
                 14644 
                 14950 
               
               
                 CD33 
                 CD33-33H4-2-vH 
                 8315 
                 11076 
                 14339 
                 14645 
                 14951 
               
               
                 CD33 
                 CD33-9C3-2-vH 
                 8316 
                 11077 
                 14340 
                 14646 
                 14952 
               
               
                 CD99 
                 CD99-hu12E7-vH 
                 8317 
                 11078 
                 14341 
                 14647 
                 14953 
               
               
                 CLL1 
                 CLL1-21C9-L2H3- 
                 8318 
                 11079 
                 14342 
                 14648 
                 14954 
               
               
                   
                 vH 
               
               
                 CLL1 
                 CLL1-6E7L4H1e-vH 
                 8319 
                 11080 
                 14343 
                 14649 
                 14955 
               
               
                 CLL1 
                 CLL1-hu1075-v1-vH 
                 8320 
                 11081 
                 14344 
                 14650 
                 14956 
               
               
                 CLL1 
                 CLL1-hu1075-v2-vH 
                 8321 
                 11082 
                 14345 
                 14651 
                 14957 
               
               
                 CS1 
                 CS1-PDL241-vH 
                 8322 
                 11083 
                 14346 
                 14652 
                 14958 
               
               
                 CS1 
                 CS1-Hu27A-vH 
                 8323 
                 11084 
                 14347 
                 14653 
                 14959 
               
               
                 CS1 
                 CS1-ScHu34C3-vH 
                 8324 
                 11085 
                 14348 
                 14654 
                 14960 
               
               
                 CS1 
                 CS1-Hu31-D2-vH 
                 8325 
                 11086 
                 14349 
                 14655 
                 14961 
               
               
                 CS1 
                 CS1-Luc34-vH 
                 8326 
                 11087 
                 14350 
                 14656 
                 14962 
               
               
                 CS1 
                 CS1-LucX2-vH 
                 8327 
                 11088 
                 14351 
                 14657 
                 14963 
               
               
                 FITC 
                 FITC-4M-53-vH 
                 8328 
                 11089 
                 14352 
                 14658 
                 14964 
               
               
                 FITC 
                 FITC-E2-vH 
                 8329 
                 11090 
                 14353 
                 14659 
                 14965 
               
               
                 GPRC5D 
                 GPRC5D-ET150-1- 
                 8330 
                 11091 
                 14354 
                 14660 
                 14966 
               
               
                   
                 vH 
               
               
                 GPRC5D 
                 GPRC5D-ET150-2- 
                 8331 
                 11092 
                 14355 
                 14661 
                 14967 
               
               
                   
                 vH 
               
               
                 HLA-A2 
                 HLA-A2-3PB2-vH 
                 8332 
                 11093 
                 14356 
                 14662 
                 14968 
               
               
                 HPV16- 
                 HPV16-7-8-vH 
                 8333 
                 11094 
                 14357 
                 14663 
                 14969 
               
               
                 E7/MHC class I 
               
               
                 HPV16- 
                 HPV16-2-vH 
                 8334 
                 11095 
                 14358 
                 14664 
                 14970 
               
               
                 E7/MHC class I 
               
               
                 Tissue Factor 1 
                 TF1-98-vH 
                 8335 
                 11096 
                 14359 
                 14665 
                 14971 
               
               
                 (TF1) 
               
               
                 Tn-Muc1 
                 Tn-Muc1-5E5-vH 
                 8336 
                 11097 
                 14360 
                 14666 
                 14972 
               
               
                 Ig Kappa-Light 
                 Kappa-LC1-vH 
                 8337 
                 11098 
                 14361 
                 14667 
                 14973 
               
               
                 Chain 
               
               
                 PTK7 
                 PTK7-7C8-vH 
                 8338 
                 11099 
                 14362 
                 14668 
                 14974 
               
               
                 PTK7 
                 PTK7-12C6a-vH 
                 8339 
                 11100 
                 14363 
                 14669 
                 14975 
               
               
                 CD19 
                 hCD19-EUK5-13-vH 
                 8340 
                 11101 
                 14364 
                 14670 
                 14976 
               
               
                 Ras/MHC class I 
                 Ras-Ab2-vH 
                 8341 
                 11102 
                 14365 
                 14671 
                 14977 
               
               
                 Ras/MHC class I 
                 Ras-Ab4-vH 
                 8342 
                 11103 
                 14366 
                 14672 
                 14978 
               
               
                 CLD18A2 
                 CLD18A2-43A11-vH 
                 8343 
                 11104 
                 14367 
                 14673 
                 14979 
               
               
                 CLD18A2 
                 CLD18A2-175D10- 
                 8344 
                 11105 
                 14368 
                 14674 
                 14980 
               
               
                   
                 vH 
               
               
                 CD43 
                 CD43-huJL-1-257- 
                 8345 
                 11106 
                 14369 
                 14675 
                 14981 
               
               
                   
                 10-vH 
               
               
                 CD69L 
                 CD69L-DREG200- 
                 8346 
                 11107 
                 14370 
                 14676 
                 14982 
               
               
                   
                 vH 
               
               
                 NY-ESO 
                 NYESO-35-15-vH 
                 8347 
                 11108 
                 14371 
                 14677 
                 14983 
               
               
                 P-glycoprotein 
                 Pgp-9F11-vH 
                 8348 
                 11109 
                 14372 
                 14678 
                 14984 
               
               
                 (MDR1) 
               
               
                 Streptag 
                 Streptag-vH 
                 8349 
                 11110 
                 14373 
                 14679 
                 14985 
               
               
                 BCMA 
                 BCMA-huC13-F12- 
                 8350 
                 11111 
                 14374 
                 14680 
                 14986 
               
               
                   
                 L1H2-v2-vH 
               
               
                 BCMA 
                 BCMA-huC12A3- 
                 8351 
                 11112 
                 14375 
                 14681 
                 14987 
               
               
                   
                 L3H3-v2-vH 
               
               
                 MPL/TPO-R 
                 Hu-161-2-vH 
                 8352 
                 11113 
                 14376 
                 14682 
                 14988 
               
               
                 P-glycoprotein 
                 Pgp-MRK16-vH 
                 8353 
                 11114 
                 14377 
                 14683 
                 14989 
               
               
                 (MDR1) 
               
               
                 CD22 
                 CD22-5-vH 
                 8354 
                 11115 
                 14378 
                 14684 
                 14990 
               
               
                 CD22 
                 CD22-10-vH 
                 8355 
                 11116 
                 14379 
                 14685 
                 14991 
               
               
                 CD22 
                 CD22-31-vH 
                 8356 
                 11117 
                 14380 
                 14686 
                 14992 
               
               
                 CD22 
                 CD22-53-vH 
                 8357 
                 11118 
                 14381 
                 14687 
                 14993 
               
               
                 CD22 
                 CD22-65-vH 
                 8358 
                 11119 
                 14382 
                 14688 
                 14994 
               
               
                 CD19 
                 hu-FMC65-1-vH 
                 8359 
                 11120 
                 14383 
                 14689 
                 14995 
               
               
                 MPL/TPO-R 
                 MPL-hu-175-2-vH 
                 8360 
                 11121 
                 14384 
                 14690 
                 14996 
               
               
                 MPL/TPO-R 
                 MPL-hu-111-2-vH 
                 8361 
                 11122 
                 14385 
                 14691 
                 14997 
               
               
                 CD179a 
                 CD179a-2460-B04- 
                 8362 
                 11123 
                 14386 
                 14692 
                 14998 
               
               
                   
                 vH 
               
               
                 CD179a 
                 CD179a-2462-E07- 
                 8363 
                 11124 
                 14387 
                 14693 
                 14999 
               
               
                   
                 vH 
               
               
                 CD37 
                 CD37-TRU-HL-vH 
                 8364 
                 11125 
                 14388 
                 14694 
                 15000 
               
               
                 CD37 
                 huCD37-Boeh-vH 
                 8365 
                 11126 
                 14389 
                 14695 
                 15001 
               
               
                 CD70 
                 CD70-13D-vH 
                 8366 
                 11127 
                 14390 
                 14696 
                 15002 
               
               
                 CD70 
                 CD70-16D-vH 
                 8367 
                 11128 
                 14391 
                 14697 
                 15003 
               
               
                 CD70 
                 CD70-21D-vH 
                 8368 
                 11129 
                 14392 
                 14698 
                 15004 
               
               
                 CD70 
                 CD70-1G2D-vH 
                 8369 
                 11130 
                 14393 
                 14699 
                 15005 
               
               
                 CD70 
                 CD70-hu-2H5-vH 
                 8370 
                 11131 
                 14394 
                 14700 
                 15006 
               
               
                 CD70 
                 CD70-69A7-vH 
                 8371 
                 11132 
                 14395 
                 14701 
                 15007 
               
               
                 CD70 
                 CD70-10B4-vH 
                 8372 
                 11133 
                 14396 
                 14702 
                 15008 
               
               
                 CD70 
                 CD70-24D-vH 
                 8373 
                 11134 
                 14397 
                 14703 
                 15009 
               
               
                 CD70 
                 CD70-25D-vH 
                 8374 
                 11135 
                 14398 
                 14704 
                 15010 
               
               
                 HIV1-env 
                 HIV1-N49P6-vH 
                 8375 
                 11136 
                 14399 
                 14705 
                 15011 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N49P7-vH 
                 8376 
                 11137 
                 14400 
                 14706 
                 15012 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N49P11-vH 
                 8377 
                 11138 
                 14401 
                 14707 
                 15013 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P1-1-vH 
                 8378 
                 11139 
                 14402 
                 14708 
                 15014 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P25-vH 
                 8379 
                 11140 
                 14403 
                 14709 
                 15015 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N49P9-vH 
                 8380 
                 11141 
                 14404 
                 14710 
                 15016 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P2-1-vH 
                 8381 
                 11142 
                 14405 
                 14711 
                 15017 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P31-1-vH 
                 8382 
                 11143 
                 14406 
                 14712 
                 15018 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P22-vH 
                 8383 
                 11144 
                 14407 
                 14713 
                 15019 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P38-vH 
                 8384 
                 11145 
                 14408 
                 14714 
                 15020 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P30-vH 
                 8385 
                 11146 
                 14409 
                 14715 
                 15021 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P36-vH 
                 8386 
                 11147 
                 14410 
                 14716 
                 15022 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P39-vH 
                 8387 
                 11148 
                 14411 
                 14717 
                 15023 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N6039-1-vH 
                 8388 
                 11149 
                 14412 
                 14718 
                 15024 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P47-vH 
                 8389 
                 11150 
                 14413 
                 14719 
                 15025 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P48-vH 
                 8390 
                 11151 
                 14414 
                 14720 
                 15026 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P51-vH 
                 8391 
                 11152 
                 14415 
                 14721 
                 15027 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P35-vH 
                 8392 
                 11153 
                 14416 
                 14722 
                 15028 
               
               
                 glycoprotein 
               
               
                 HIV1-env 
                 HIV1-N60P37-vH 
                 8393 
                 11154 
                 14417 
                 14723 
                 15029 
               
               
                 glycoprotein 
               
               
                 Lym1 
                 hu-Lym1-vH 
                 8394 
                 11155 
                 14418 
                 14724 
                 15030 
               
               
                 Lym2 
                 hu-Lym2-vH 
                 8395 
                 11156 
                 14419 
                 14725 
                 15031 
               
               
                 BCMA 
                 BCMA-USC1-vH 
                 8396 
                 11157 
                 14420 
                 14726 
                 15032 
               
               
                 BCMA 
                 BCMA-USC2-vH 
                 8397 
                 11158 
                 14421 
                 14727 
                 15033 
               
               
                 BCMA 
                 BCMA-USC3-vH 
                 8398 
                 11159 
                 14422 
                 14728 
                 15034 
               
               
                 BCMA 
                 BCMA-USC4-vH 
                 8399 
                 11160 
                 14423 
                 14729 
                 15035 
               
               
                 BCMA 
                 BCMA-USC5-vH 
                 8400 
                 11161 
                 14424 
                 14730 
                 15036 
               
               
                 BCMA 
                 BCMA-USC6-vH 
                 8401 
                 11162 
                 14425 
                 14731 
                 15037 
               
               
                 BCMA 
                 BCMA-USC7-vH 
                 8402 
                 11163 
                 14426 
                 14732 
                 15038 
               
               
                 CD43 
                 CD43-huJL-1-257- 
                 8403 
                 11164 
                 14427 
                 14733 
                 15039 
               
               
                   
                 10-vH 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6C 
               
             
            
               
                   
               
               
                 scFV Fragments 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                 SEQ 
                 SEQ 
                   
                   
                 SEQ 
                 SEQ 
               
               
                   
                   
                 ID- 
                 ID- 
                   
                   
                 ID- 
                 ID- 
               
               
                 Target 
                 NAME 
                 DNA 
                 PRT 
                 Target 
                 NAME 
                 DNA 
                 PRT 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 CD19 
                 FMC63 
                 8404 
                 11165 
                 CDH17 
                 CDH17- 
                 8443 
                 11204 
               
               
                   
                   
                   
                   
                   
                 PTA001A4 
               
               
                 CD19 
                 huFMC63- 
                 8405 
                 11166 
                 CDH19 
                 CDH19- 
                 8444 
                 11205 
               
               
                   
                 11 
                   
                   
                   
                 16A4 
               
               
                 CD19 
                 CD19Bu12 
                 8406 
                 11167 
                 EGFR 
                 Cetuximab 
                 8445 
                 11206 
               
               
                 CD19 
                 CD19MM 
                 8407 
                 11168 
                 CLEC5A 
                 CLEC5A- 
                 8446 
                 11207 
               
               
                   
                   
                   
                   
                   
                 8H8F5 
               
               
                 CD19 
                 CD19-4G7 
                 8408 
                 11169 
                 CLEC5A 
                 CLEC5A- 
                 8447 
                 11208 
               
               
                   
                   
                   
                   
                   
                 3E12A2 
               
               
                 HIV1-env 
                 HIV1-N6 
                 8409 
                 11170 
                 CLL1 
                 CLL1-M26 
                 8448 
                 11209 
               
               
                 ALK 
                 Alk-48 
                 8410 
                 11171 
                 CLL1 
                 CLL1-M32 
                 8449 
                 11210 
               
               
                 ALK 
                 Alk-58 
                 8411 
                 11172 
                 CMVpp65 
                 CMVpp65- 
                 8450 
                 11211 
               
               
                   
                   
                   
                   
                   
                 F5 
               
               
                 Amyloid 
                 Amyloid- 
                 8412 
                 11173 
                 CS1 
                 CS1- 
                 8451 
                 11212 
               
               
                   
                 158 
                   
                   
                   
                 huLuc63 
               
               
                 CD45 
                 BC8-CD45 
                 8413 
                 11174 
                 CS1 
                 CS1- 
                 8452 
                 11213 
               
               
                   
                   
                   
                   
                   
                 HuLuc64 
               
               
                 BCMA 
                 BCMA- 
                 8414 
                 11175 
                 CS1 
                 CS1- 
                 8453 
                 11214 
               
               
                   
                 J6M0 
                   
                   
                   
                 huLuc90 
               
               
                 BCMA 
                 BCMA- 
                 8415 
                 11176 
                 CSF2RA 
                 CSF2RA- 
                 8454 
                 11215 
               
               
                   
                 huC12A3- 
                   
                   
                   
                 Ab6 
               
               
                   
                 L3H3 
               
               
                 BCMA 
                 BCMA- 
                 8416 
                 11177 
                 CSF2RA 
                 CSF2RA- 
                 8455 
                 11216 
               
               
                   
                 ET-40 
                   
                   
                   
                 Ab1 
               
               
                 BCMA 
                 BCMA- 
                 8417 
                 11178 
                 DLL3 
                 DLL3- 
                 8456 
                 11217 
               
               
                   
                 ET-54 
                   
                   
                   
                 hSC16-13 
               
               
                 CCR4 
                 CCR4- 
                 8418 
                 11179 
                 DLL3 
                 DLL3- 
                 8457 
                 11218 
               
               
                   
                 humAb1567 
                   
                   
                   
                 hSC16-56 
               
               
                 CD5 
                 CD5-9 
                 8419 
                 11180 
                 EBNA3c 
                 EBNA3c- 
                 8458 
                 11219 
               
               
                   
                   
                   
                   
                   
                 315 
               
               
                 CD5 
                 CD5-18 
                 8420 
                 11181 
                 Ebv-gp350 
                 EBV- 
                 8459 
                 11220 
               
               
                   
                   
                   
                   
                   
                 gp350 
               
               
                 CD20 
                 CD20-2F2 
                 8421 
                 11182 
                 EGFRviii 
                 EGFRvIII- 
                 8460 
                 11221 
               
               
                   
                   
                   
                   
                   
                 139 
               
               
                 CD20 
                 CD20- 
                 8422 
                 11183 
                 EGFRviii 
                 EGFRvIII- 
                 8461 
                 11222 
               
               
                   
                 GA101 
                   
                   
                   
                 2173 
               
               
                 CD22 
                 CD22- 
                 8423 
                 11184 
                 EpCam1 
                 Epcam1- 
                 8462 
                 11223 
               
               
                   
                 h10F4v2 
                   
                   
                   
                 MM1 
               
               
                 CD22 
                 CD22- 
                 8424 
                 11185 
                 EpCam1 
                 Epcam1- 
                 8463 
                 11224 
               
               
                   
                 H22Rhov2 
                   
                   
                   
                 D5K5 
               
               
                   
                 ACDRKA 
               
               
                 CD22 
                 CD22- 
                 8425 
                 11186 
                 FLT3 
                 FLT3-NC7 
                 8464 
                 11225 
               
               
                   
                 m971 
               
               
                 CD30 
                 CD30- 
                 8426 
                 11187 
                 FITC 
                 FITC 
                 8465 
                 11226 
               
               
                   
                 5F11 
               
               
                 CD30 
                 CD30- 
                 8427 
                 11188 
                 Influenza 
                 FLU- 
                 8466 
                 11227 
               
               
                   
                 Ac10 
                   
                   
                 A HA 
                 MEDI- 
               
               
                   
                   
                   
                   
                   
                 8852 
               
               
                 CD32 
                 CD32- 
                 8428 
                 11189 
                 FR1 
                 FR1- 
                 8467 
                 11228 
               
               
                   
                 Med9 
                   
                   
                   
                 huMov19 
               
               
                 CD33 
                 CD33-AF5 
                 8429 
                 11190 
                 GAD 
                 GAD- 
                 8468 
                 11229 
               
               
                   
                   
                   
                   
                   
                 G3H8 
               
               
                 CD33 
                 CD33- 
                 8430 
                 11191 
                 GD2 
                 GD2-hu14- 
                 8469 
                 11230 
               
               
                   
                 huMyc9 
                   
                   
                   
                 18 
               
               
                 CD34 
                 CD34- 
                 8431 
                 11192 
                 GD2 
                 GD2- 
                 8470 
                 11231 
               
               
                   
                 hu4C7 
                   
                   
                   
                 hu3F8 
               
               
                 CD44v6 
                 CD44v6- 
                 8432 
                 11193 
                 GD3 
                 GD3-KM- 
                 8471 
                 11232 
               
               
                   
                 Biwa8 
                   
                   
                   
                 641 
               
               
                 CD70 
                 CD70- 
                 8433 
                 11194 
                 GFRa4 
                 GFRAlpha 
                 8472 
                 11233 
               
               
                   
                 h1F6 
                   
                   
                   
                 4-P4-6 
               
               
                 CD79b 
                 CD79b- 
                 8434 
                 11195 
                 GFRa4 
                 GFRa4-P4- 
                 8473 
                 11234 
               
               
                   
                 2F2 
                   
                   
                   
                 10 
               
               
                 CD123 
                 CD123- 
                 8435 
                 11196 
                 GM1 
                 GM1-5B2 
                 8474 
                 11235 
               
               
                   
                 CSL362 
               
               
                 CD138 
                 CD138 
                 8436 
                 11197 
                 GM1 
                 GM1-7E5 
                 8475 
                 11236 
               
               
                 CD179b 
                 CD179b 
                 8437 
                 11198 
                 GPRC5D 
                 GPRC5D- 
                 8476 
                 11237 
               
               
                   
                   
                   
                   
                   
                 ET150-5 
               
               
                 CD276 
                 CD276-17 
                 8438 
                 11199 
                 GPRC5D 
                 GPRC5D- 
                 8477 
                 11238 
               
               
                   
                   
                   
                   
                   
                 ET150-18 
               
               
                 CD324 
                 CD324- 
                 8439 
                 11200 
                 gp100 
                 gp100 
                 8478 
                 11239 
               
               
                   
                 SC10-6 
               
               
                 CD324 
                 CD324- 
                 8440 
                 11201 
                 gp100 
                 gp100- 
                 8479 
                 11240 
               
               
                   
                 hSC10-17 
                   
                   
                   
                 G2D12 
               
               
                 CDH6 
                 CDH6- 
                 8441 
                 11202 
                 GPC3 
                 GPC3-4E5 
                 8480 
                 11241 
               
               
                   
                 NOV710 
               
               
                 CDH6 
                 CDH6- 
                 8442 
                 11203 
                 gpNMB 
                 gpNMB- 
                 8481 
                 11242 
               
               
                   
                 NOV712 
                   
                   
                   
                 115 
               
               
                 GRP78 
                 GRP78- 
                 8482 
                 11243 
                 PDL1 
                 PDL1- 
                 8522 
                 11283 
               
               
                   
                 GC18 
                   
                   
                   
                 SP142 
               
               
                 HIV1- 
                 HIV1-E5 
                 8483 
                 11244 
                 PDL1 
                 PDL1- 
                 8523 
                 11284 
               
               
                 gag(77-85) 
                   
                   
                   
                   
                 10A5 
               
               
                 HIV1-env 
                 HIV1- 
                 8484 
                 11245 
                 PSCA 
                 PSCA- 
                 8524 
                 11285 
               
               
                   
                 3BNC117 
                   
                   
                   
                 Ha14-121 
               
               
                 HIV1-env 
                 HIV1- 
                 8485 
                 11246 
                 PSCA 
                 PSCA- 
                 8525 
                 11286 
               
               
                   
                 PGT-128 
                   
                   
                   
                 Ha14-117 
               
               
                 HIV1-env 
                 HIV1-VR- 
                 8486 
                 11247 
                 PR1 
                 PR1 
                 8526 
                 11287 
               
               
                   
                 C01 
               
               
                 HIV1-env 
                 HIV1-X5 
                 8487 
                 11248 
                 PSMA 
                 PSMA-006 
                 8527 
                 11288 
               
               
                 HMW- 
                 HMW- 
                 8488 
                 11249 
                 PSMA 
                 PSMA- 
                 8528 
                 11289 
               
               
                 MAA 
                 MAA- 
                   
                   
                   
                 J591 
               
               
                   
                 hIND 
               
               
                 HTLV1- 
                 HTLV- 
                 8489 
                 11250 
                 PTK7 
                 PTK7- 
                 8529 
                 11290 
               
               
                 TAX 
                 TAX-T3F2 
                   
                   
                   
                 hSC6-23 
               
               
                 HTLV1- 
                 HTLV- 
                 8490 
                 11251 
                 PTK7 
                 PTK7- 
                 8530 
                 11291 
               
               
                 TAX 
                 TAX-T3E3 
                   
                   
                   
                 SC6-10-2 
               
               
                 IL11Ra 
                 IL11Ra- 
                 8491 
                 11252 
                 ROR1 
                 ROR1-4A5 
                 8531 
                 11292 
               
               
                   
                 8E2-Ts107 
               
               
                 IL13Ra2 
                 IL13Ra2- 
                 8492 
                 11253 
                 ROR1 
                 ROR1- 
                 8532 
                 11293 
               
               
                   
                 hu107 
                   
                   
                   
                 4C10 
               
               
                 IL13Ra2 
                 IL13Ra2- 
                 8493 
                 11254 
                 Mesothelin 
                 SD1-vHH- 
                 8533 
                 11294 
               
               
                   
                 Hul08 
                   
                   
                   
                 Linker- 
               
               
                   
                   
                   
                   
                   
                 SD2-vHH 
               
               
                 KSHV- 
                 KSHV-4C3 
                 8494 
                 11255 
                 SLea 
                 SLea-7E3 
                 8534 
                 11295 
               
               
                 K8.1 
               
               
                 LAMP1 
                 LAMP1- 
                 8495 
                 11256 
                 SLea 
                 SLea-5B1 
                 8535 
                 11296 
               
               
                   
                 humabl-2 
               
               
                 LAMP1 
                 LAMP1- 
                 8496 
                 11257 
                 SSEA4 
                 SSEA4 
                 8536 
                 11297 
               
               
                   
                 Mb4 
               
               
                 LewisY 
                 LewisY- 
                 8497 
                 11258 
                 TCRB1 
                 TCRB1- 
                 8537 
                 11298 
               
               
                   
                 huS193 
                   
                   
                   
                 CP01-E09 
               
               
                 L1CAM 
                 L1CAM-9- 
                 8498 
                 11259 
                 TCRB1 
                 TCRB1- 
                 8538 
                 11299 
               
               
                   
                 3-HU3 
                   
                   
                   
                 Jovi1 
               
               
                 Lym1 
                 Lym1 
                 8499 
                 11260 
                 TCRB2 
                 TCRB2- 
                 8539 
                 11300 
               
               
                   
                   
                   
                   
                   
                 CP01-D05 
               
               
                 Lym2 
                 Lym2 
                 8500 
                 11261 
                 TCRB2 
                 TCRB2- 
                 8540 
                 11301 
               
               
                   
                   
                   
                   
                   
                 CP01-E05 
               
               
                 CD79b 
                 huMA79bv 
                 8501 
                 11262 
                 TCRgd 
                 TCRgd- 
                 8541 
                 11302 
               
               
                   
                 28 
                   
                   
                   
                 G5-4 
               
               
                 MART1 
                 MART1-CAG10 
                 8502 
                 11263 
                 TERT 
                 TERT- 
                 8542 
                 11303 
               
               
                   
                   
                   
                   
                   
                 4A9-T540 
               
               
                 MART1 
                 MART1- 
                 8503 
                 11264 
                 TERT 
                 TERT- 
                 8543 
                 11304 
               
               
                   
                 CLA12 
                   
                   
                   
                 3G3-T865 
               
               
                 Mesothelin 
                 Mesothelin- 
                 8504 
                 11265 
                 TGFBR2 
                 TGFBR2- 
                 8544 
                 11305 
               
               
                   
                 m912 
                   
                   
                   
                 Ab1 
               
               
                 MPL 
                 MPL-175 
                 8505 
                 11266 
                 TIM1 
                 TIM1- 
                 8545 
                 11306 
               
               
                   
                   
                   
                   
                   
                 HVCR1- 
               
               
                   
                   
                   
                   
                   
                 270-2 
               
               
                 MPL 
                 MPL-161 
                 8506 
                 11267 
                 TIM1 
                 TIM1- 
                 8546 
                 11307 
               
               
                   
                   
                   
                   
                   
                 HVCR1- 
               
               
                   
                   
                   
                   
                   
                 ARD5 
               
               
                 MPL 
                 MPL-161- 
                 8507 
                 11268 
                 TnAg 
                 TnAg 
                 8547 
                 11308 
               
               
                   
                 HL 
               
               
                 MPL 
                 MPL-111 
                 8508 
                 11269 
                 Tn-Muc1 
                 TnMuc1- 
                 8548 
                 11309 
               
               
                   
                   
                   
                   
                   
                 hu5E5- 
               
               
                   
                   
                   
                   
                   
                 RHA8- 
               
               
                   
                   
                   
                   
                   
                 RKA-2 
               
               
                 MPL 
                 MPL-178 
                 8509 
                 11270 
                 TROP2 
                 TROP2- 
                 8549 
                 11310 
               
               
                   
                   
                   
                   
                   
                 ARA47- 
               
               
                   
                   
                   
                   
                   
                 HV3KV3 
               
               
                 MPL 
                 MPL- 
                 8510 
                 11271 
                 TROP2 
                 TROP2- 
                 8550 
                 11311 
               
               
                   
                 AB317 
                   
                   
                   
                 h7E6-SVG 
               
               
                 MPL 
                 MPL- 
                 8511 
                 11272 
                 TSHR 
                 TSHR-K1- 
                 8551 
                 11312 
               
               
                   
                 12E10 
                   
                   
                   
                 70 
               
               
                 MPL 
                 MPL- 
                 8512 
                 11273 
                 TSHR 
                 TSHR- 
                 8552 
                 11313 
               
               
                   
                 huVB22B 
                   
                   
                   
                 KB1 
               
               
                   
                 w5 
               
               
                 Muc1 
                 Muc1-D6- 
                 8513 
                 11274 
                 TSHR 
                 TSHR-5C9 
                 8553 
                 11314 
               
               
                   
                 M3B8 
               
               
                 Muc1 
                 MUC1-D6- 
                 8514 
                 11275 
                 TSLRP 
                 TSLRP 
                 8554 
                 11315 
               
               
                   
                 M3A1 
               
               
                 Muc16 
                 Muc16- 
                 8515 
                 11276 
                 Tyrosinase 
                 Tyros-B2 
                 8555 
                 11316 
               
               
                   
                 4H11 
               
               
                 EGFR 
                 Nimotuzumab 
                 8516 
                 11277 
                 Tyrosinase 
                 Tyros-MC1 
                 8556 
                 11317 
               
               
                 NKG2D 
                 NKG2D- 
                 8517 
                 11278 
                 Tyrosinase 
                 Tyros-TA2 
                 8557 
                 11318 
               
               
                   
                 MS 
               
               
                 NYBR1 
                 NYBR1 
                 8518 
                 11279 
                 VEGFR3 
                 VEGFR3- 
                 8558 
                 11319 
               
               
                   
                   
                   
                   
                   
                 Ab1 
               
               
                 NY-ESO 
                 NYESO- 
                 8519 
                 11280 
                 WT1 
                 WT1-Ab1 
                 8559 
                 11320 
               
               
                   
                 T1 
               
               
                 NY-ESO 
                 NYESO- 
                 8520 
                 11281 
                 WT1 
                 WT1-Ab5 
                 8560 
                 11321 
               
               
                   
                 T1 
               
               
                 PDL1 
                 PDL1- 
                 8521 
                 11282 
                 WT1 
                 WT1-Ab13 
                 8561 
                 11322 
               
               
                   
                 Atezoli 
               
               
                 WT1 
                 WT1-Ab15 
                 8562 
                 11323 
                 CD22 
                 CD22-65 
                 8658 
                 11356 
               
               
                 CD123 
                 CD123- 
                 8563 
                 11324 
                 CD19 
                 hu-FMC65 
                 8659 
                 11357 
               
               
                   
                 1172 
               
               
                 CDH19 
                 CDH19- 
                 8564 
                 11325 
                 MPL 
                 MPL-hu- 
                 8660 
                 11358 
               
               
                   
                 4B10 
                   
                   
                   
                 175-2 
               
               
                 FRbeta 
                 FRbeta- 
                 8565 
                 11326 
                 MPL 
                 MPL-hu- 
                 8661 
                 11359 
               
               
                   
                 m923 
                   
                   
                   
                 111-2 
               
               
                 LHR-8B7 
                 LHR-8B7 
                 8566 
                 11327 
                 CD179a 
                 CD179a- 
                 8662 
                 11360 
               
               
                   
                   
                   
                   
                   
                 2460-B04 
               
               
                 LHR-5F4- 
                 LHR-5F4- 
                 8567 
                 11328 
                 CD179a 
                 CD179a- 
                 8663 
                 11361 
               
               
                 21 
                 21 
                   
                   
                   
                 2462-E07 
               
               
                 B7H4 
                 B7H4- 
                 8568 
                 11329 
                 CD37 
                 CD37- 
                 8664 
                 11362 
               
               
                   
                 hu22C10 
                   
                   
                   
                 TRU-HL 
               
               
                 B7H4- 
                 B7H4- 
                 8569 
                 11330 
                 CD37 
                 huCD37- 
                 8665 
                 11363 
               
               
                 hu1D11 
                 hu1D11 
                   
                   
                   
                 Boeh 
               
               
                 IgE 
                 IgE- 
                 8570 
                 11331 
                 CD70 
                 CD70-13D 
                 8666 
                 11364 
               
               
                   
                 omalizumab 
               
               
                 CD23 
                 CD23- 
                 8571 
                 11332 
                 CD70 
                 CD70-16D 
                 8667 
                 11365 
               
               
                   
                 p5E8 
               
               
                 GCC 
                 GCC-5F9 
                 8572 
                 11333 
                 CD70 
                 CD70-21D 
                 8668 
                 11366 
               
               
                 GCC 
                 GCC- 
                 8573 
                 11334 
                 CD70 
                 CD70- 
                 8669 
                 11367 
               
               
                   
                 Ab229 
                   
                   
                   
                 1G2D 
               
               
                 CD200R 
                 CD200R- 
                 8637 
                 11335 
                 CD70 
                 CD70- 
                 8670 
                 11368 
               
               
                   
                 huDx182 
                   
                   
                   
                 hu2H5 
               
               
                 Tn-Muc1- 
                 Tn-Muc1- 
                 8638 
                 11336 
                 CD70 
                 CD70- 
                 8671 
                 11369 
               
               
                 5E5 
                 5E5 
                   
                   
                   
                 69A7 
               
               
                 Igk-Light 
                 Kappa-LC1 
                 8639 
                 11337 
                 CD70 
                 CD70- 
                 8672 
                 11370 
               
               
                 Chain 
                   
                   
                   
                   
                 10B4 
               
               
                 PTK7 
                 PTK7-7C8 
                 8640 
                 11338 
                 CD70 
                 CD70-24D 
                 8673 
                 11371 
               
               
                 PTK7 
                 PTK7- 
                 8641 
                 11339 
                 CD70 
                 CD70-25D 
                 8674 
                 11372 
               
               
                   
                 12C6a 
               
               
                 CD19 
                 hCD19- 
                 8642 
                 11340 
                 HIV1-env 
                 HIV1- 
                 8675 
                 11373 
               
               
                   
                 EUK5-13 
                   
                   
                   
                 N49P6 
               
               
                 Ras 
                 Ras-Ab2 
                 8643 
                 11341 
                 HIV1-env 
                 HIV1- 
                 8676 
                 11374 
               
               
                   
                   
                   
                   
                   
                 N49P7 
               
               
                 Ras 
                 Ras-Ab4 
                 8644 
                 11342 
                 HIV1-env 
                 HIV1- 
                 8677 
                 11375 
               
               
                   
                   
                   
                   
                   
                 N49P11 
               
               
                 CLD18A2 
                 CLD18A2- 
                 8645 
                 11343 
                 HIV1-env 
                 HIV1- 
                 8678 
                 11376 
               
               
                   
                 43A11 
                   
                   
                   
                 N60P1-1 
               
               
                 CLD18A2 
                 CLD18A2- 
                 8646 
                 11344 
                 HIV1-env 
                 HIV1- 
                 8679 
                 11377 
               
               
                   
                 175D10 
                   
                   
                   
                 N60P25 
               
               
                 CD43 
                 CD43- 
                 8647 
                 11345 
                 HIV1-env 
                 HIV1- 
                 8680 
                 11378 
               
               
                   
                 huJL-1- 
                   
                   
                   
                 N49P9 
               
               
                   
                 257-10 
               
               
                 CD69L 
                 CD69L- 
                 8648 
                 11346 
                 HIV1-env 
                 HIV1- 
                 8681 
                 11379 
               
               
                   
                 DREG200 
                   
                   
                   
                 N60P2-1 
               
               
                 NY-ESO 
                 NYESO- 
                 8649 
                 11347 
                 HIV1-env 
                 HIV1- 
                 8682 
                 11380 
               
               
                   
                 35-15 
                   
                   
                   
                 N60P31-1 
               
               
                 Pgp 
                 Pgp-9F11 
                 8650 
                 11348 
                 HIV1-env 
                 HIV1- 
                 8683 
                 11381 
               
               
                   
                   
                   
                   
                   
                 N60P22 
               
               
                 Streptag 
                 Streptag 
                 8651 
                 11349 
                 HIV1-env 
                 HIV1- 
                 8684 
                 11382 
               
               
                   
                   
                   
                   
                   
                 N60P38 
               
               
                 MPL 
                 Hu-161-2 
                 8652 
                 11350 
                 HIV1-env 
                 HIV1- 
                 8685 
                 11383 
               
               
                   
                   
                   
                   
                   
                 N60P30 
               
               
                 Pgp 
                 Pgp- 
                 8653 
                 11351 
                 HIV1-env 
                 HIV1- 
                 8686 
                 11384 
               
               
                   
                 MRK16 
                   
                   
                   
                 N60P36 
               
               
                 CD22 
                 CD22-5 
                 8654 
                 11352 
                 HIV1-env 
                 HIV1- 
                 8687 
                 11385 
               
               
                   
                   
                   
                   
                   
                 N60P39 
               
               
                 CD22 
                 CD22-10 
                 8655 
                 11353 
                 HIV1-env 
                 HIV1- 
                 8688 
                 11386 
               
               
                   
                   
                   
                   
                   
                 N6039.1 
               
               
                 CD22 
                 CD22-31 
                 8656 
                 11354 
                 HIV1-env 
                 HIV1- 
                 8689 
                 11387 
               
               
                   
                   
                   
                   
                   
                 N60P47 
               
               
                 CD22 
                 CD22-53 
                 8657 
                 11355 
                 HIV1-env 
                 HIV1- 
                 8690 
                 11388 
               
               
                   
                   
                   
                   
                   
                 N60P48 
               
               
                 HIV1-env 
                 HIV1- 
                 8691 
                 11389 
                 BCMA 
                 BCMA- 
                 8698 
                 11396 
               
               
                   
                 N60P51 
                   
                   
                   
                 USC3 
               
               
                 HIV1-env 
                 HIV1- 
                 8692 
                 11390 
                 BCMA 
                 BCMA- 
                 8699 
                 11397 
               
               
                   
                 N60P35 
                   
                   
                   
                 USC4 
               
               
                 HIV1-env 
                 HIV1- 
                 8693 
                 11391 
                 BCMA 
                 BCMA- 
                 8700 
                 11398 
               
               
                   
                 N60P37 
                   
                   
                   
                 USC5 
               
               
                 Lym1 
                 hu-Lym1 
                 8694 
                 11392 
                 BCMA 
                 BCMA- 
                 8701 
                 11399 
               
               
                   
                   
                   
                   
                   
                 USC6 
               
               
                 Lym2 
                 hu-Lym2 
                 8695 
                 11393 
                 BCMA 
                 BCMA- 
                 8702 
                 11400 
               
               
                   
                   
                   
                   
                   
                 USC7 
               
               
                 BCMA 
                 BCMA- 
                 8696 
                 11394 
                 CD33 
                 CD33- 
                 8727 
                 15099 
               
               
                   
                 USC1 
                   
                   
                   
                 SGNh2H12 
               
               
                 BCMA 
                 BCMA- 
                 8697 
                 11395 
                 CD33 
                 CD33- 
                 8728 
                 15100 
               
               
                   
                 USC2 
                   
                   
                   
                 15G15-33 
               
               
                 CD19 
                 CD19- 
                 8698 
                 15070 
                 CD33 
                 CD33- 
                 8729 
                 15101 
               
               
                   
                 MEDI- 
                   
                   
                   
                 33H4 
               
               
                   
                 3649 
               
               
                 CD19 
                 CD19- 
                 8699 
                 15071 
                 CD33 
                 CD33-9C3- 
                 8730 
                 15102 
               
               
                   
                 Medrex- 
                   
                   
                   
                 2 
               
               
                   
                 24D1 
               
               
                 CD19 
                 CD8SP- 
                 8700 
                 15072 
                 CD99 
                 CD99- 
                 8731 
                 15103 
               
               
                   
                 Ritx- 
                   
                   
                   
                 hu12E7 
               
               
                   
                 CD19- 
               
               
                   
                 MOR0028 
               
               
                 CD19 
                 CD19- 
                 8701 
                 15073 
                 CD123 
                 CD123- 
                 8732 
                 15104 
               
               
                   
                 HD37- 
                   
                   
                   
                 DART1-1 
               
               
                   
                 H2L1 
               
               
                 CD19 
                 CD19- 
                 8702 
                 15074 
                 CD123 
                 CD123- 
                 8733 
                 15105 
               
               
                   
                 huBly3 
                   
                   
                   
                 DART1-2 
               
               
                 CD19 
                 CD19- 
                 8703 
                 15075 
                 CD123 
                 CD123- 
                 8734 
                 15106 
               
               
                   
                 huSJ25C1 
                   
                   
                   
                 I3RB18 
               
               
                 CD19 
                 CD8SP- 
                 8704 
                 15076 
                 CD123 
                 CD123- 
                 8735 
                 15107 
               
               
                   
                 Ritx- 
                   
                   
                   
                 hu3E3 
               
               
                   
                 CD19-hB4 
               
               
                 CD19 
                 CD19-hu- 
                 8705 
                 15077 
                 CD123 
                 CD123- 
                 8736 
                 15108 
               
               
                   
                 mR005-1 
                   
                   
                   
                 9F6 
               
               
                 CD19 
                 CD19- 
                 8706 
                 15078 
                 CD123 
                 CD123- 
                 8737 
                 15109 
               
               
                   
                 hA19 
                   
                   
                   
                 I3RB2 
               
               
                 AFP/MHC 
                 AFP-61 
                 8707 
                 15079 
                 CD123 
                 CD123- 
                 8738 
                 15110 
               
               
                 I 
                   
                   
                   
                   
                 1176 
               
               
                 AFP/MHC 
                 AFP-76 
                 8708 
                 15080 
                 CD123 
                 CD8SP- 
                 8739 
                 15111 
               
               
                 I 
                   
                   
                   
                   
                 Ritx2- 
               
               
                   
                   
                   
                   
                   
                 CD123- 
               
               
                   
                   
                   
                   
                   
                 8B11 
               
               
                 AFP/MHC 
                 AFP-79 
                 8709 
                 15081 
                 CD123 
                 CD123- 
                 8740 
                 15112 
               
               
                 I 
                   
                   
                   
                   
                 2B8 
               
               
                 BCMA 
                 BCMA- 
                 8710 
                 15082 
                 CD123 
                 CD123- 
                 8741 
                 15113 
               
               
                   
                 ET-03 
                   
                   
                   
                 9D7 
               
               
                 BCMA 
                 BCMA- 
                 8711 
                 15083 
                 CD123 
                 CD123- 
                 8742 
                 15114 
               
               
                   
                 huC11.D5.3L1H3 
                   
                   
                   
                 3B10 
               
               
                 BCMA 
                 BCMA- 
                 8712 
                 15084 
                 CLL1 
                 CLL1- 
                 8743 
                 15115 
               
               
                   
                 huC13-F12 
                   
                   
                   
                 21C9- 
               
               
                   
                   
                   
                   
                   
                 L2H3 
               
               
                 CD20 
                 CD20- 
                 8713 
                 15085 
                 CLL1 
                 CLL1- 
                 8744 
                 15116 
               
               
                   
                 11B8 
                   
                   
                   
                 6E7L4H1e 
               
               
                 CD20 
                 CD20-2C6 
                 8714 
                 15086 
                 CLL1 
                 CLL1- 
                 8745 
                 15117 
               
               
                   
                   
                   
                   
                   
                 hu1075-v1 
               
               
                 CD20 
                 CD20-2H7 
                 8715 
                 15087 
                 CLL1 
                 CLL1- 
                 8746 
                 15118 
               
               
                   
                   
                   
                   
                   
                 hu1075-v2 
               
               
                 CD20 
                 CD20- 
                 8716 
                 15088 
                 CS1 
                 CS1- 
                 8747 
                 15119 
               
               
                   
                 hA20 
                   
                   
                   
                 PDL241 
               
               
                 CD20 
                 CD20-BM- 
                 8717 
                 15089 
                 CS1 
                 CS1- 
                 8748 
                 15120 
               
               
                   
                 CA-1925- 
                   
                   
                   
                 Hu27A 
               
               
                   
                 v4 
               
               
                 CD20 
                 CD20- 
                 8718 
                 15090 
                 CS1 
                 CS1- 
                 8749 
                 15121 
               
               
                   
                 Ubli-v4 
                   
                   
                   
                 ScHu34C3 
               
               
                 CD20 
                 CD20-2H7 
                 8719 
                 15091 
                 CS1 
                 CS1-Hu31- 
                 8750 
                 15122 
               
               
                   
                   
                   
                   
                   
                 D2 
               
               
                 CD20 
                 CD20- 
                 8720 
                 15092 
                 CS1 
                 CS1-Luc34 
                 8751 
                 15123 
               
               
                   
                 h1F5 
               
               
                 CD20 
                 CD20-7D8 
                 8721 
                 15093 
                 CS1 
                 CS1- 
                 8752 
                 15124 
               
               
                   
                   
                   
                   
                   
                 LucX2 
               
               
                 CD20 
                 CD20- 
                 8722 
                 15094 
                 FITC 
                 FITC-4M- 
                 8753 
                 15125 
               
               
                   
                 7D8-vL- 
                   
                   
                   
                 53 
               
               
                   
                 linker-GA- 
               
               
                   
                 Tag-VH 
               
               
                 CD20 
                 CD20- 
                 8723 
                 15095 
                 FITC 
                 FITC-E2- 
                 8754 
                 15126 
               
               
                   
                 AME-33 
                   
                   
                   
                 HL 
               
               
                 CD43 
                 CD43- 
                 8703 
                 11401 
                 GPRC5D 
                 GPRC5D- 
                 8755 
                 15127 
               
               
                   
                 huJL-1- 
                   
                   
                   
                 ET150-1 
               
               
                   
                 257-10 
               
               
                 CD22 
                 CD22- 
                 8724 
                 15096 
                 GPRC5D 
                 GPRC5D- 
                 8756 
                 15128 
               
               
                   
                 m971-HL 
                   
                   
                   
                 ET150-2 
               
               
                 CD33 
                 CD8SP- 
                 8725 
                 15097 
                 HLA-A2 
                 HLA-A2- 
                 8757 
                 15129 
               
               
                   
                 Ritx2- 
                   
                   
                   
                 3PB2 
               
               
                   
                 BC33- 
               
               
                   
                 Boehr2800308 
               
               
                 CD33 
                 CD8SP- 
                 8726 
                 15098 
                 HPV16/MHC 
                 HPV16-7-8 
                 8758 
                 15130 
               
               
                   
                 Ritx2- 
                   
                   
                 I 
               
               
                   
                 CD33- 
               
               
                   
                 Him3-4 
               
               
                 TF1 
                 TF1-98 
                 8760 
                 15132 
                 HPV16/MHC 
                 HPV16-2 
                 8759 
                 15131 
               
               
                   
                   
                   
                   
                 I 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6D 
               
             
            
               
                   
               
               
                 CAR COMPONENTS 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 SEQ 
                 SEQ 
                   
                 SEQ 
                 SEQ 
               
               
                   
                 ID NO 
                 ID NO 
                   
                 ID NO 
                 ID NO 
               
               
                 CAR component 
                 (DNA) 
                 (PRT) 
                 CAR component 
                 (DNA) 
                 (PRT) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 F2A 
                 925 
                 4838 
                 IgG1-CH1-TCRd-6MD 
                 962 
                 4875 
               
               
                 T2A 
                 926 
                 4839 
                 IgG1-CH1-TCRa-SDVP- 
                 963 
                 4876 
               
               
                   
                   
                   
                 6MD 
                   
                   
               
               
                 P2A 
                 928 
                 4841 
                 IgG1-CH1-TCRa-wt2-opt- 
                 964 
                 4877 
               
               
                   
                   
                   
                 6MD 
                   
                   
               
               
                 E2A 
                 930 
                 4843 
                 hTCRa-WT 
                 3885 
                 15041 
               
               
                 SGSG Linker 
                 931 
                 4844 
                 hTCRa-CSDVP 
                 3886 
                 15042 
               
               
                 FURINE SITE 
                 933 
                 4846 
                 hTCRa-opt2 
                 3887 
                 15043 
               
               
                 hCD8-Hinge-TM 
                 936 
                 4849 
                 hTCRa-T48C-opt 
                 3889 
                 15045 
               
               
                 hCD8-Hinge-TM-BBz 
                 937 
                 4850 
                 hTCRa-S61R 
                 3892 
                 15048 
               
               
                 4-1BB-cytosolic-domain 
                 939 
                 4852 
                 hTCR-b1-constant 
                 3895 
                 15051 
               
               
                 CD3z-cytosolic-domain 
                 940 
                 4853 
                 hTCR-b2-constant 
                 3896 
                 15052 
               
               
                 CD28-Hinge-TM-CP 
                 942 
                 4855 
                 hTCRb-WT 
                 3897 
                 15053 
               
               
                 CD3d-ECDTMCP-opt2 
                 944 
                 4857 
                 hTCRb-S57C-opt1 
                 3898 
                 15054 
               
               
                 CD3eECDTMCP-opt2 
                 948 
                 4861 
                 hTCRb-KACIAH 
                 3899 
                 15055 
               
               
                 CD3g-ECDTMCP-opt2 
                 949 
                 4862 
                 hTCRb-opt2 
                 3900 
                 15056 
               
               
                 CD3zECDTMCP-opt2 
                 958 
                 4871 
                 hTCRb-R79G 
                 3910 
                 15066 
               
               
                 IgCL-TCRg-6MD 
                 959 
                 4872 
                 hTCRg-(hTCR-gamma) 
                 3912 
                 15068 
               
               
                 IgCL-TCRb-IAH-6MD 
                 960 
                 4873 
                 hTCR-(hTCR-delta) 
                 3913 
                 15069 
               
               
                 IgCL-TCRb-wt2-opt- 
                 961 
                 4874 
                 CD8-Signal-Peptide 
                 1 
                 3914 
               
               
                 6MD 
                   
                   
                   
                   
                   
               
               
                 IgH-Signal Peptide 
                 5 
                 3918 
                 (GGGGS)x3_LINKER 
                 278 
                 4191 
               
               
                 Myc-Tag 
                 903 
                 4816 
                 V5 Tag 
                 908 
                 4821 
               
               
                 RiTX2-TAG 
                 918 
                 4831 
                 RITX4 TAG 
                 919 
                 4832 
               
               
                 PG4SP 
                 288 
                 4201 
                 EAAAK 
                 292 
                 4205 
               
               
                 PG4SP-v2-U 
                 289 
                 4202 
                 EAAAK-v2 
                 293 
                 4206 
               
               
                 E-coil 
                 290 
                 4203 
                 K-coil 
                 291 
                 4204 
               
               
                 TCRa-opt-6MD 
                 15141 
                 15133 
                 TCRg-6MD 
                 15143 
                 15135 
               
               
                 TCRb-opt-6MD 
                 15142 
                 15134 
                 TCRd-6MD 
                 15144 
                 15136 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 EXEMPLARY ACCESSORY MODULES 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 SEQ 
                 SEQ 
                   
                 SEQ 
                 SEQ 
               
               
                   
                 ID NO 
                 ID NO 
                   
                 ID NO 
                 ID NO 
               
               
                 Accessory Module 
                 (DNA) 
                 (PRT) 
                 Accessory Module 
                 (DNA) 
                 (PRT) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 K13-opt 
                 7768 
                 10538 
                 IKK1-S176E-S180E 
                 1004 
                 4917 
               
               
                 K13-vFLIP 
                 972 
                 4885 
                 FKBPx2-hNEMO-K277A 
                 1006 
                 4919 
               
               
                 FKBP-K13 
                 973 
                 4886 
                 FKBPx2-hNEMO- 
                 1007 
                 4920 
               
               
                   
                   
                   
                 L753(251) 
                   
                   
               
               
                 FKBPX2-K13 
                 974 
                 4887 
                 FKBPx2-hNEMO- 
                 1008 
                 4921 
               
               
                   
                   
                   
                 L600(200) 
                   
                   
               
               
                 Myr-FKBPx2-K13 
                 975 
                 4888 
                 FKBPx2-RIP-ID 
                 1009 
                 4922 
               
               
                 FKBPx2-HTLV2-Tax-RS 
                 976 
                 4889 
                 hNEMO-FL-GS- 
                 7763 
                 10533 
               
               
                   
                   
                   
                 FKBPv36X2 
                   
                   
               
               
                 FKBPx2-Flag-HTLV2- 
                 977 
                 4890 
                 hNEMO-L825-GS- 
                 7764 
                 10534 
               
               
                 Tax-RS 
                   
                   
                 FKBPv36x2 
                   
                   
               
               
                 hNEMO-K277A 
                 979 
                 4892 
                 hNEMO-L753-GS- 
                 7765 
                 10535 
               
               
                   
                   
                   
                 FKBPv36x2 
                   
                   
               
               
                 hNEMO-D23V-K277A 
                 980 
                 4893 
                 hNEMO-L600-GS- 
                 7766 
                 10536 
               
               
                   
                   
                   
                 FKBPv36x2 
                   
                   
               
               
                 hNEMO-K277A-L1161 
                 986 
                 4899 
                 hNEMO-K277A-Delta- 
                 7767 
                 10537 
               
               
                   
                   
                   
                 V249-K255 
                   
                   
               
               
                 hNEMO-K277A-L1014 
                 989 
                 4902 
                 IKK1-delta-SCD- 
                 7781 
                 10541 
               
               
                   
                   
                   
                 FKBPv36x2 
                   
                   
               
               
                 mNEMO-K270A 
                 992 
                 4905 
                 IKK2-delta-SCD- 
                 7782 
                 10542 
               
               
                   
                   
                   
                 FKBPv36x2 
                   
                   
               
               
                 RIP-ID 
                 998 
                 4911 
                 TCL-1A 
                 1005 
                 4918 
               
               
                 MyD88 
                 999 
                 4912 
                 MTCP-1 
                 7769 
                 10539 
               
               
                 MYD88-L265P 
                 1000 
                 4913 
                 CMV-141 
                 7770 
                 10540 
               
               
                 IKK2 
                 1001 
                 4914 
                 IgSP-[hTRAC-opt2] 
                 1010 
                 4923 
               
               
                 IKK2-S177E-S181E 
                 1002 
                 4915 
                 IgSP-[hTRBC-opt2] 
                 1011 
                 4924 
               
               
                 IKK1 
                 1003 
                 4916 
                   
                   
                   
               
               
                 IgSP-TCRa-opt-6MD 
                 15145 
                 15137 
                 IgSP-TCRg-6MD 
                 15147 
                 15139 
               
               
                 IgSP-TCRb-opt-6MD 
                 15146 
                 15138 
                 IgSP-TCRd-6MD 
                 15148 
                 15140 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 MHC I (HLA-A2) restricted peptides used for generation of CARs 
               
            
           
           
               
               
               
            
               
                   
                 Protein/Epitope 
                 SEQ ID NO: 
               
               
                   
               
               
                   
                 gp100 
                 10511 
               
               
                   
                 gp100 
                 10512 
               
               
                   
                 gp100 
                 10513 
               
               
                   
                 MUC1-A7 (130-138) 
                 10514 
               
               
                   
                 MUC1-D6 (13-21) 
                 10515 
               
               
                   
                 TAX (11-19) 
                 10516 
               
               
                   
                 hTERT(540-548) 
                 10517 
               
               
                   
                 hTERT (865-873) 
                 10518 
               
               
                   
                 HIV1 gag (77-85) 
                 10519 
               
               
                   
                 CMV-pp65(495-503) 
                 10520 
               
               
                   
                 MART (26-35) 
                 10521 
               
               
                   
                 EBNA-3A (596-604) 
                 10522 
               
               
                   
                 EBNA-3c 
                 10523 
               
               
                   
                 WT1 
                 10524 
               
               
                   
                 PR1 
                 10525 
               
               
                   
                 Ras9-G12V 
                 10526 
               
               
                   
                 HPV16-E7 
                 10527 
               
               
                   
                 NY-ESO-1-(155-163) 
                 10528 
               
               
                   
                 NY-ESO-1-(157-165) 
                 10529 
               
               
                   
                 NY-ESO-1-(157-167) 
                 10530 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 9 
               
               
                   
               
               
                   
                 EXEMPLARY DISEASE TARGETED BY CARs (i.e. conventional 
               
               
                 CAR/BiTE “X” 
                 CARs and next generation CARs. E.g., SIR, Ab-TCR, and TFP) and 
               
               
                 TARGET 
                 Bispecific T Cell Engagers (BiTE) 
               
               
                   
               
             
            
               
                 CD19 
                 ALL, CLL, lymphoma, lymphoid blast crisis of CML, multiple myeloma, 
               
               
                   
                 immune disorders 
               
               
                 ALK 
                 Non Small Cell Lung Cancer (NSCLC), ALCL (anaplastic large cell 
               
               
                   
                 lymphoma), IMT (inflammatory myofibroblastic tumor), or nemoblastoma 
               
               
                 CD45 
                 Blood cancers 
               
               
                 BCMA 
                 Myeloma, PEL, plasma cell leukemia, Waldenstrom&#39;s macroglobinemia 
               
               
                 CD5 
                 Blood cancer, T cell leukemia, T cell lymphoma 
               
               
                 CD20 
                 Blood cancers, Leukemia, ALL, CLL, lymphoma, immune disorders 
               
               
                 CD22 
                 Blood cancers, Leukemia, ALL, CLL, lymphoma, lymphoid blast crisis of 
               
               
                   
                 CML, immune disorders 
               
               
                 CD23 
                 Blood cancers, Leukemia, ALL, CLL, lymphoma, autoimmune disorders 
               
               
                 CD30 
                 Hodgkins&#39;s lymphoma, Cutaneous T cell lymphoma 
               
               
                 CD32 
                 Solid tumors 
               
               
                 CD33 
                 Blood cancers, AML, MDS 
               
               
                 CD34 
                 Blood cancers, AML, MDS 
               
               
                 CD44v6 
                 Blood cancers, AML, MDS 
               
               
                 CD70 
                 Blood cancers, lymphoma, myeloma, Waldenstrom&#39;s macroglobulinemia, 
               
               
                   
                 Kidney cancer 
               
               
                 CD79b 
                 Blood cancers, ALL, Lymphoma 
               
               
                 CD123 
                 Blood cancers, AML, MDS 
               
               
                 CD138 
                 Blood cancers, Myeloma, PEL, plasma cell leukemia, waldenstrom&#39;s 
               
               
                   
                 macroglobulinemia 
               
               
                 CD179b 
                 Blood cancers, ALL, Lymphoma 
               
               
                 CD276/B7-H3 
                 Ewing&#39;s sarcoma, neuroblastoma, rhabdomyosarcoma, ovarian, colorectal and 
               
               
                   
                 lung cancers 
               
               
                 CD324 
                 Solid tumors, esophageal, prostate, colorectal, breast, lung cancers 
               
               
                 CDH6 
                 Solid tumors, renal, ovarian, thyroid cancers 
               
               
                 CDH17 
                 Adenocarciniomas, gastrointestinal, lung, ovarian, endometrial cancers 
               
               
                 CDH19 
                 Solid tumor, Melanoma 
               
               
                 EGFR 
                 Colon cancer, lung cancer 
               
               
                 CLEC5A 
                 Blood cancers, Leukemia, AML 
               
               
                 GR/LHR 
                 Prostate cancer, ovarian cancer or breast cancer 
               
               
                 CLL1 
                 Blood cancer, Leukemia 
               
               
                 CMVpp65 
                 CMV infection, CMV colitis, CMV pneumonitis 
               
               
                 CS1 
                 Blood cancers, myeloma, PEL, plasma cell leukemia 
               
               
                 CSF2RA 
                 AML, CML, MDS 
               
               
                 CD123 
                 Blood cancers, AML, MDS 
               
               
                 DLL3 
                 Melanoma, lung cancer or ovarian cancer 
               
               
                 EBNA3c/MHC I 
                 Epstein Barr virus infection and related diseases including cancers 
               
               
                 EBV-gp350 
                 Epstein Barr virus infection and related diseases 
               
               
                 EGFR 
                 Solid tumors, Colon cancer, lung cancer 
               
               
                 EGFRvIII 
                 Solid tumors, glioblastoma 
               
               
                 EpCam1 
                 Gastrointestinal cancer 
               
               
                 FLT3 
                 Blood cancers, AML, MDS, ALL 
               
               
                 Folate Receptor 
                 Ovarian cancer, NSCLC, endometrial cancer, renal cancer, or other solid 
               
               
                 alpha(FR1 or 
                 tumors 
               
               
                 FOLR1) 
                   
               
               
                 FSHR 
                 Prostate cancer, ovarian cancer or breast cancer 
               
               
                 GD2 
                 Neuroblastoma 
               
               
                 GD3 
                 Melanoma 
               
               
                 GFRa4 
                 Cancer, thyroid medullary cancer 
               
               
                 Fucosyl- 
                 Small cell lung cancer 
               
               
                 GM1(GM1) 
                   
               
               
                 GPRC5D 
                 Myeloma, PEL, plasma cell leukemia, waldenstrom&#39;s macroglobulinemia 
               
               
                 gp100 
                 Melanoma 
               
               
                 GPC3 
                 Solid tumors, Lung cancer 
               
               
                 gpNMB 
                 Melanoma, brain tumors, gastric cancers 
               
               
                 GRP78 
                 Myeloma 
               
               
                 Her2 
                 Solid tumors, breast cancer, stomach cancer 
               
               
                 Her3 
                 Colorectal, breast cancer 
               
               
                 HMW-MAA 
                 Melanoma 
               
               
                 HTLV1- 
                 HTLV1 infection associated diseases, Adult T cell leukemia-lymphoma 
               
               
                 TAX/MHC I 
                   
               
               
                 IL11Ra 
                 Blood cancers, AML, ALL, CML, MDS, sarcomas 
               
               
                 IL6Ra 
                 Solid tumors, Liver cancer 
               
               
                 IL13Ra2 
                 Glioblastomas 
               
               
                 KSHV-K8.1 
                 Kaposi&#39;s sarcoma, PEL, Multicentric Castleman&#39;s disease 
               
               
                 LAMP1 
                 Blood cancers, AML, ALL, MDS, CLL, CML 
               
               
                 LewisY 
                 Cancers 
               
               
                 L1CAM 
                 Solid tumors, ovarian, breast, endometrial cancers, melanoma 
               
               
                 LHR 
                 Prostate cancer, ovarian cancer or breast cancer 
               
               
                 Lym1 
                 Blood cancer, Leukemia, Lymphoma 
               
               
                 Lym2 
                 Blood cancer, Leukemia, Lymphoma 
               
               
                 CD79b 
                 Blood cancers, lymphoma 
               
               
                 MART1/MHC I 
                 Melanoma 
               
               
                 Mesothelin 
                 Mesothelioma, ovarian cancer, pancreatic cancer 
               
               
                 Muc1/MHC I 
                 Breast cancer, gastric cancer, colorectal cancer, lung cancer, or other solid 
               
               
                   
                 tumors 
               
               
                 Muc16 
                 Ovarian cancer 
               
               
                 NKG2D 
                 Leukemia, lymphoma or myeloma 
               
               
                 NYBR1 
                 Breast cancer 
               
               
                 PSCA 
                 Prostate cancer 
               
               
                 PR1/MHC I 
                 Blood cancer, Leukemia 
               
               
                 Prolactin 
                 Breast cancer, chromophobe renal cell cancer 
               
               
                 Receptor 
                   
               
               
                 PSMA 
                 Prostate cancer 
               
               
                 PTK7 
                 Melanoma, lung cancer or ovarian cancer 
               
               
                 ROR1 
                 Blood cancer, B cell malignancy, lymphoma, CLL 
               
               
                 SLea 
                 Pancreatic cancer, colon cancer 
               
               
                 SSEA4 
                 Pancreatic cancer 
               
               
                 Tyrosinase/MHC 
                 Melanoma 
               
               
                 I 
                   
               
               
                 TCRB1 
                 T cell leukemias and lymphomas, autoimmune disorders 
               
               
                 TCRB2 
                 T cell leukemias and lymphomas, autoimmune disorders 
               
               
                 TCRgd 
                 T cell leukemias and lymphomas, autoimmune disorders 
               
               
                 hTERT 
                 Solid tumors, blood cancers 
               
               
                 TGFBR2 
                 Solid tumors, keloid 
               
               
                 TIM1/HAVCR1 
                 Kidney cancer, liver cancer 
               
               
                 TROP2 
                 Solid tumors, Breast cancer, prostate cancer 
               
               
                 TSHR 
                 Thyroid cancer, T cell leukemia, T cell Lymphoma 
               
               
                 TSLPR 
                 Blood cancers, Leukemias, AML, MDS 
               
               
                 Tyrosinase/MHC 
                 Melanoma 
               
               
                 I 
                   
               
               
                 VEGFR3 
                 Solid tumors 
               
               
                 WT1/MHC I 
                 Blood cancers, AML 
               
               
                 Folate Receptorβ 
                 AML, Myeloma 
               
               
                 B7H4 
                 Breast cancer or ovarian cancer 
               
               
                 CD23 
                 Blood cancers, Leukemias, CLL 
               
               
                 GCC 
                 Gastrointestinal cancer 
               
               
                 CD200R 
                 Blood cancers, AML, MDS 
               
               
                 AFP/MHC I 
                 Solid tumors, Liver cancer 
               
               
                 CD99 
                 Liver cancer 
               
               
                 GPRC5D 
                 Myeloma, waldenstrom&#39;s macroglobinemia 
               
               
                 HPV16-E7/MHC 
                 HPV16 associated cancers, cervical cancer, head and neck cancers 
               
               
                 I 
                   
               
               
                 Tissue Factor 1 
                 Solid tumors 
               
               
                 (TF1) 
                   
               
               
                 Tn-Muc1 
                 Solid tumors and blood cancers 
               
               
                 Igk-Light Chain 
                 Myeloma, plasma cell leukemia 
               
               
                 Ras G12V/MHC 
                 Solid tumors and blood cancers 
               
               
                 I 
                   
               
               
                 CLD18A2 
                 Gastric, pancreatic, esophageal, ovarian, or lung cancer 
               
               
                 (Claudin 18.2) 
                   
               
               
                 CD43 
                 Blood cancers, AML 
               
               
                 NY-ESO-1/MHC 
                 Myeloma 
               
               
                 I 
                   
               
               
                 MPL/TPO-R 
                 Blood cancer, AML, MDS, CML, ALL 
               
               
                 P-glycoprotein 
                 Renal cancer, liver cancer, Myeloma 
               
               
                 (MDR1) 
                   
               
               
                 CD179a 
                 Blood cancers, Acute Leukemia, CLL, ALL, Lymphoma 
               
               
                 STEAP1 
                 Gastric or prostate cancer, or lymphoma 
               
               
                 Liv1 (SLC39A6) 
                 Breast or prostate cancer 
               
               
                 Nectin4 (PVRL4) 
                 Bladder, renal, cervical, lung, head and neck or breast cancer 
               
               
                 Cripto (TDGF1) 
                 Colorectal or endometrial or ovarian cancer 
               
               
                 gpA33 
                 Colorectal or endometrial or ovarian cancer 
               
               
                 FLT3 
                 Blood cancers, AML, ALL, MDS 
               
               
                 BST1/CD157 
                 Blood cancers, AML, MDS 
               
               
                 IL1RAP 
                 Liver, colorectal, cervical, lung or ovarian cancer 
               
               
                 Chloride channel 
                 Glioma 
               
               
                 IgE 
                 Allergy 
               
               
                 HLA-A2 
                 Graft vs host disease, tissue rejection (SIR Expressed in regulatory T cells) 
               
               
                 Amyloid 
                 Amyloidoses, alzheimer&#39;s disease 
               
               
                 HIV1-env 
                 HIVI/AIDS and related conditions 
               
               
                 HIV1-gag 
                 HIV1/AIDS and related conditions 
               
               
                 Influenza A HA 
                 Influenza A infection 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Exemplary CARs Targeting HIV-1 Envelop Glycoprotein 
               
               
                 Based on HIV1-N49P6 vL and vH binding domains 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                 SEQ 
                 SEQ 
               
               
                   
                 Accessory 
                   
                 ID NO 
                 ID NO 
               
               
                 CAR TYPE 
                 Module 
                 CAR NAME 
                 (DNA) 
                 (PRT) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 2nd Gen CAR 
                 None 
                 CD8SP-HIV1-N49P6-vL-Gly-Ser- 
                 8704 
                 11402 
               
               
                   
                   
                 Linker-HIV1-N49P6-vH-Myc-CD8TM- 
                   
                   
               
               
                   
                   
                 BBz 
                   
                   
               
               
                 2nd Gen CAR 
                 None 
                 CD8SP-HIV1-N49P6-vH-Gly-Ser- 
                 8705 
                 11403 
               
               
                   
                   
                 Linker-vL-Myc-CD8TM-BBz 
                   
                   
               
               
                 1st Gen CAR 
                 vFLIP-K13 
                 CD8SP-HIV1-N49P6-vL-Gly-Ser- 
                 8706 
                 11404 
               
               
                   
                   
                 Linker-HIV1-N49P6-vH-Myc-CD8TM- 
                   
                   
               
               
                   
                   
                 z-P2A-K13 
                   
                   
               
               
                 1st Gen CAR 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vL-vH)-Myc-z- 
                 8707 
                 11405 
               
               
                   
                   
                 P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vL-vH)-CD3e- 
                 8708 
                 11406 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vL-vH)-CD3d- 
                 8709 
                 11407 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vL-vH)-CD3g- 
                 8710 
                 11408 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vL-vH)-CD3z- 
                 8711 
                 11409 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vH-vL)-CD3e- 
                 8712 
                 11410 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vH-vL)-CD3d- 
                 8713 
                 11411 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vH-vL)-CD3g- 
                 8714 
                 11412 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 TFP 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-(vH-vL)-CD3z- 
                 8715 
                 11413 
               
               
                   
                   
                 ECDTMCP-opt2-P2A-hNEMO-K277A 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-[hTCRb- 
                 8716 
                 11414 
               
               
                   
                   
                 KACIAH]-F-P2A-SP-HIV1-N49P6- 
                   
                   
               
               
                   
                   
                 vH-[hTCRa-CSDVP] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-[hTCRa- 
                 8717 
                 11415 
               
               
                   
                   
                 CSDVP]-F-F2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                   
                 [hTCRb-KACIAH] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-PG4SP-v2- 
                 8718 
                 11416 
               
               
                   
                   
                 [hTCRb-KACIAH]-F-P2A-SP-HIV1- 
                   
                   
               
               
                   
                   
                 N49P6-vH-PG4SP-[hTCRa-CSDVP] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-E-Coil- 
                 8719 
                 11417 
               
               
                   
                   
                 [hTCRb-KACIAH]-F-P2A-SP-HIV1- 
                   
                   
               
               
                   
                   
                 N49P6-vH-K-Coil-[hTCRa-CSDVP] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-EAAAK- 
                 8720 
                 11418 
               
               
                   
                   
                 [hTCRb-KACIAH]-F-P2A-SP-HIV1- 
                   
                   
               
               
                   
                   
                 N49P6-vH-EAAAK-v2-[hTCRa- 
                   
                   
               
               
                   
                   
                 CSDVP] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-V5-[hTCRb- 
                 8721 
                 11419 
               
               
                   
                   
                 KACIAH]-F-P2A-SP-HIV1-N49P6- 
                   
                   
               
               
                   
                   
                 vH-Myc4-[hTCRa-CSDVP] 
                   
                   
               
               
                 DC SIR 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-vL-[hTCRb- 
                 8722 
                 11420 
               
               
                   
                   
                 KACIAH]-F-P2A-SP-HIV1-N49P6- 
                   
                   
               
               
                   
                   
                 vH-[hTCRa-CSDVP]-F-F2A-hNEMO- 
                   
                   
               
               
                   
                   
                 K277A 
                   
                   
               
               
                 DC SIR 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-vL-[hTCRa- 
                 8723 
                 11421 
               
               
                   
                   
                 CSDVP]-F-F2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                   
                 [hTCRb-KACIAH]-F-P2A-hNEMO- 
                   
                   
               
               
                   
                   
                 K277A 
                   
                   
               
               
                 Ab-TCR 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-vL-[IgCL-TCRg- 
                 8724 
                 11422 
               
               
                   
                   
                 6MD]-F-P2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                   
                 [IgG1-CH1-TCRd-6MD]-F-F2A- 
                   
                   
               
               
                   
                   
                 hNEMO-K277A 
                   
                   
               
               
                 Ab-TCR 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-vL-[IgCL-TCRb- 
                 8725 
                 11423 
               
               
                   
                   
                 IAH-6MD]-F-P2A-SP-HIV1-N49P6- 
                   
                   
               
               
                   
                   
                 vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
                   
                   
               
               
                   
                   
                 F2A-hNEMO-K277A 
                   
                   
               
               
                 Ab-TCR 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-vL-[IgCL-TCRb- 
                 8726 
                 11424 
               
               
                   
                   
                 wt2-opt-6MD]-F-P2A-SP-HIV1- 
                   
                   
               
               
                   
                   
                 N49P6-vH-[IgG1-CH1-TCRa-wt2-opt- 
                   
                   
               
               
                   
                   
                 6MD]-F-F2A-hNEMO-K277A 
                   
                   
               
               
                 1st Gen CAR 
                 hNEMO-K277A- 
                 CD8SP-HIV1-N49P6-vL-Gly-Ser- 
                 8727 
                 11425 
               
               
                   
                 Delta-V249- 
                 Linker-HIV1-N49P6-vH--CD8TM-z- 
                   
                   
               
               
                   
                 K255 
                 P2A-hNEMO-K277A-Delta-V249- 
                   
                   
               
               
                   
                   
                 K255 
                   
                   
               
               
                 1st Gen CAR 
                 IKK2-S177E- 
                 CD8SP-HIV1-N49P6-vL-Gly-Ser- 
                 8728 
                 11426 
               
               
                   
                 S181E 
                 Linker-HIV1-N49P6-vH--CD8TM-z- 
                   
                   
               
               
                   
                   
                 P2A-IKK2-S177E-S181E 
                   
                   
               
               
                 DC SIR 
                 hNEMO-K277A 
                 CD8SP-HIV1-N49P6-vL-[hTCRa- 
                 8729 
                 11427 
               
               
                   
                   
                 T48C]-F-F2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                   
                 [hTCRb-S57C]-F-P2A-hNEMO- 
                   
                   
               
               
                   
                   
                 K277A 
                   
                   
               
               
                 DC SIR 
                 IKK1-S176E- 
                 CD8SP-HIV1-N49P6-vL-[hTCRb- 
                 8730 
                 11428 
               
               
                   
                 S180E 
                 S57C]-F-P2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                   
                 [hTCRa-T48C]-F-F2A-IKK1-S176E- 
                   
                   
               
               
                   
                   
                 S180E 
                   
                   
               
               
                 DC SIR 
                 hNEMO-K277A- 
                 CD8SP-HIV1-N49P6-vL-[hTCRb- 
                 8731 
                 11429 
               
               
                   
                 Delta-V249- 
                 S57C]-F-P2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                 K255 
                 [hTCRa-T48C]-F-F2A-hNEMO- 
                   
                   
               
               
                   
                   
                 K277A-Delta-V249-K255 
                   
                   
               
               
                 OHC SIR 
                 None 
                 CD8SP-MYC-[hTCRa-T48C-opt1]-F- 
                 8732 
                 11430 
               
               
                   
                   
                 F2A-SP-HIV1-N49P6-vL-Gly-Ser- 
                   
                   
               
               
                   
                   
                 Linker-HIV1-N49P6-vH-V5-[hTCRb- 
                   
                   
               
               
                   
                   
                 S57C-opt1] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-V5-[hTCRb- 
                 8733 
                 11431 
               
               
                   
                   
                 S57C-opt]-F-P2A-SP-HIV1-N49P6- 
                   
                   
               
               
                   
                   
                 vH-Myc-[hTCRa-T48C-opt] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-[hTCRb- 
                 8734 
                 11432 
               
               
                   
                   
                 opt2]-F-P2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                   
                 [hTCRa-opt2] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-[hTCRb- 
                 8735 
                 11433 
               
               
                   
                   
                 opt2]-F-P2A-SP-HIV1-N49P6-vH- 
                   
                   
               
               
                   
                   
                 Myc-[preTCRa-Del48] 
                   
                   
               
               
                 OHC SIR 
                 None 
                 CD8SP-[hTCRb-opt2]-F-P2A-CD8SP- 
                 8736 
                 11434 
               
               
                   
                   
                 HIV1-N49P6-vL-Gly-Ser-Linker- 
                   
                   
               
               
                   
                   
                 HIV1-N49P6-vH-Myc4-[preTCRa- 
                   
                   
               
               
                   
                   
                 Del48] 
                   
                   
               
               
                 DC SIR 
                 None 
                 CD8SP-HIV1-N49P6-vL-V5-[hTCRg1- 
                 8737 
                 11435 
               
               
                   
                   
                 opt]-F-P2A-SP-HIV1-N49P6-vH-Myc- 
                   
                   
               
               
                   
                   
                 [hTCRd-opt] 
               
               
                   
               
            
           
         
       
     
     Abbreviations; 1st Gen CAR, First Generation CAR; 2nd Gen CAR, 2nd Generation CAR; DC SIR, Double Chain SIR; OHC SIR, One half chain SIR. 
     The accessory modules in the above exemplary constructs in Table 10 are optional and can be deleted or replaced by other accessory modules. 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 SEQ ID NOs OF CARs CONTAINING DIFFERENT ANTIGEN BINDING DOMAINS 
               
               
                 USING SEQ ID NOs OF CARS WITH HIV1-N49P6 AS REFERENCE 
               
            
           
           
               
               
               
               
            
               
                   
                 Antigen binding 
                 CAR SEQ ID NOs 
                 CAR SEQ ID NO 
               
               
                 Target Antigen 
                 domain 
                 (DNA) 
                 (PRT) 
               
               
                   
               
               
                 HIV1 Env 
                 HIV1-N49P6 
                 8704-8737 
                 11402-11435 
               
               
                 HIV1 Env 
                 HIV1-N49P7 
                 8738-8771 
                 11436-11469 
               
               
                 HIV1 Env 
                 HIV1-N49P11 
                 8806-8839 
                 11504-11537 
               
               
                 HIV1 Env 
                 HIV1-N60P1-1 
                 8840-8873 
                 11538-11571 
               
               
                 HIV1 Env 
                 HIV1-N60P25 
                 8942-8975 
                 11640-11673 
               
               
                 HIV1 Env 
                 HIV1-N49P9 
                 8772-8805 
                 11470-11503 
               
               
                 HIV1 Env 
                 HIV1-N60P2-1 
                 8874-8907 
                 11572-11605 
               
               
                 HIV1 Env 
                 HIV1-N60P31-1 
                 9010-9043 
                 11708-11741 
               
               
                 HIV1 Env 
                 HIV1-N60P22 
                 8908-8941 
                 11606-11639 
               
               
                 HIV1 Env 
                 HIV1-N60P38 
                 9146-9179 
                 11844-11877 
               
               
                 HIV1 Env 
                 HIV1-N60P30 
                 8976-9009 
                 11674-11707 
               
               
                 HIV1 Env 
                 HIV1-N60P36 
                 9078-9111 
                 11776-11809 
               
               
                 HIV1 Env 
                 HIV1-N60P39 
                 9180-9213 
                 11878-11911 
               
               
                 HIV1 Env 
                 HIV1-N6039-1 
                 9316-9349 
                 12014-12047 
               
               
                 HIV1 Env 
                 HIV1-N60P47 
                 9214-9247 
                 11912-11945 
               
               
                 HIV1 Env 
                 HIV1-N60P48 
                 9248-9281 
                 11946-11979 
               
               
                 HIV1 Env 
                 HIV1-N60P51 
                 9282-9315 
                 11980-12013 
               
               
                 HIV1 Env 
                 HIV1-N60P35 
                 9044-9077 
                 11742-11775 
               
               
                 HIV1 Env 
                 HIV1-N60P37 
                 9112-9145 
                 11810-11843 
               
               
                 Lym1 
                 hu-Lym1 
                 10370-10403 
                 13068-13101 
               
               
                 Lym2 
                 hu-Lym2 
                 10404-10437 
                 13102-13135 
               
               
                 BCMA 
                 BCMA-USC1 
                 9418-9451 
                 12116-12149 
               
               
                 BCMA 
                 BCMA-USC2 
                 9452-9485 
                 12150-12183 
               
               
                 BCMA 
                 BCMA-USC3 
                 9486-9519 
                 12184-12217 
               
               
                 BCMA 
                 BCMA-USC4 
                 9520-9554 
                 12218-12252 
               
               
                 BCMA 
                 BCMA-USC5 
                 9555-9587 
                 12253-12285 
               
               
                 BCMA 
                 BCMA-USC6 
                 9588-9621 
                 12286-12319 
               
               
                 BCMA 
                 BCMA-USC7 
                 9622-9655 
                 12320-12353 
               
               
                 CD43 
                 CD43-huJL-1-257-10 
                 9758-9791 
                 12456-12489 
               
               
                 BCMA 
                 BCMA- 
                 9350-9383 
                 12048-12081 
               
               
                   
                 huC11.D5.3L1H3 
                   
                   
               
               
                 BCMA 
                 BCMA-huC13-F12 
                 9384-9417 
                 12082-12115 
               
               
                 CD20 
                 CD20-Ubli-v4 
                 9656-9689 
                 12354-12387 
               
               
                 CD37 
                 CD37-TRU-HL 
                 9724-9757 
                 12422-12455 
               
               
                 CD70 
                 CD70-1G2D 
                 9792-9825 
                 12490-12523 
               
               
                 CD70 
                 CD70-10B4 
                 9826-9859 
                 12524-12557 
               
               
                 CD70 
                 CD70-13D 
                 9860-9893 
                 12558-12591 
               
               
                 CD70 
                 CD70-16D 
                 9894-9927 
                 12592-12625 
               
               
                 CD70 
                 CD70-21D 
                 9928-9961 
                 12626-12659 
               
               
                 CD70 
                 CD70-24D 
                 9962-9995 
                 12660-12693 
               
               
                 CD70 
                 CD70-25D 
                  9996-10029 
                 12694-12727 
               
               
                 CD70 
                 CD70-69A7 
                 10030-10063 
                 12728-12761 
               
               
                 CD70 
                 CD70-hu-2H5 
                 10064-10097 
                 12762-12795 
               
               
                 CD123 
                 CD123-DART-1 
                 10098-10131 
                 12796-12829 
               
               
                 CD123 
                 CD123-DART-2 
                 10132-10165 
                 12830-12863 
               
               
                 CD179a 
                 CD179a-2460-B04 
                 10166-10199 
                 12864-12897 
               
               
                 CD179a 
                 CD179a-2462-E07 
                 10200-10233 
                 12898-12931 
               
               
                 FITC 
                 FITC-4M-53 
                 10234-10267 
                 12932-12965 
               
               
                 FITC 
                 FITC-E2 
                 10268-10301 
                 12966-12999 
               
               
                 MPL 
                 Hu-161-2 
                 10302-10335 
                 13000-13033 
               
               
                 CD37 
                 huCD37-Boeh 
                 10336-10369 
                 13034-13067 
               
               
                 Kappa-Light Chain 
                 Kappa-LC1 
                 10438-10471 
                 13136-13169 
               
               
                 MPL 
                 MPL-hu-111-2 
                 10472-10505 
                 13170-13203 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 Exemplary Ist Generation CAR constructs coexpressing hNEMO-K277A 
               
               
                 and PAC accessory modules. Both accessory modules are optional. 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 SEQ 
                 SEQ 
               
               
                   
                 Name of CAR constructs including the name of 
                 ID NO 
                 ID NO 
               
               
                 Target 
                 antigen binding domain 
                 (DNA) 
                 (PRT) 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 CD19 
                 CD8SP-FMC63-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1594 
                 5507 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-huFMC63-11-(vL-vH)-Myc-z-P2A- 
                 1595 
                 5508 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-huFMC63-11-N203Q-(vL-vH)-Myc-z- 
                 1596 
                 5509 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19Bul2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1597 
                 5510 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-2-CD19MM-(vL-vH)-Myc-z-P2A- 
                 1598 
                 5511 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-4G7-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1599 
                 5512 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-MEDI-3649-(vL-vH)-Myc-z-P2A- 
                 1600 
                 5513 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-Medrex-24D1-(vL-vH)-Myc-z-P2A- 
                 1601 
                 5514 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-Ritx-CD19-MOR0028-(vL-vH)-Myc-z- 
                 1602 
                 5515 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-HD37-H2L1-(vL-vH)-Myc-z-P2A- 
                 1603 
                 5516 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-huBly3-(vL-vH)-Myc-z-P2A- 
                 1604 
                 5517 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-huSJ25C1-(vL-vH)-Myc-z-P2A- 
                 1605 
                 5518 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-Ritx-CD19-hB4-(vL-vH)-Myc-z-P2A- 
                 1606 
                 5519 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-hu-mROO5-1-(vL-vH)-Myc-z-P2A- 
                 1607 
                 5520 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-hA19-(vL-vH)-Myc-z-P2A- 
                 1608 
                 5521 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 AFP/MHC class I 
                 CD8SP-AFP-61-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1609 
                 5522 
               
               
                 complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 AFP/MHC class I 
                 CD8SP-AFP-76-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1610 
                 5523 
               
               
                 complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 AFP/MHC class I 
                 CD8SP-AFP-79-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1611 
                 5524 
               
               
                 complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HIV1-envelop 
                 CD8SP-HIV1-N6-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1612 
                 5525 
               
               
                 glycoprotein 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 ALK 
                 CD8SP-Alk-48-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1613 
                 5526 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 ALK 
                 CD8SP-Alk-58-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1614 
                 5527 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Amyloid 
                 SP-Amyloid-158-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1615 
                 5528 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Biotin 
                 CD8SP-dc-Avidin-Myc-z-P2A-hNEMO-K277A- 
                 1616 
                 5529 
               
               
                   
                 Flag-T2A-PAC 
                   
                   
               
               
                 CD45 
                 CD8SP-BC8-CD45-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1617 
                 5530 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-J6M0-(vL-vH)-Myc-z-P2A- 
                 1618 
                 5531 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-huC12A3-L3H3-(vL-vH)-Myc-z- 
                 1619 
                 5532 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-ET-40-(vL-vH)-Myc-z-P2A- 
                 1620 
                 5533 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-ET-54-(vL-vH)-Myc-z-P2A- 
                 1621 
                 5534 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-ET-03-(vL-vH)-Myc-z-P2A- 
                 1622 
                 5535 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-huC11.D5.3L1H3-(vL-vH)-Myc-z- 
                 1623 
                 5536 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-huC13-F12-(vL-vH)-Myc-z-P2A- 
                 1624 
                 5537 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CCR4 
                 CD8SP-CCR4-humAbl567-(vL-vH)-Myc-z-P2A- 
                 1625 
                 5538 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HIV1-envelop 
                 CD8SP-CD4-ECD-Linker-DC-SIGN-Myc-z-P2A- 
                 1626 
                 5539 
               
               
                 glycoprotein 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD5 
                 CD8SP-CD5-9-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1627 
                 5540 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD5 
                 CD8SP-CD5-18-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1628 
                 5541 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Ig Fc 
                 CD8SP-CD16A-V158-ECD-v2-Myc-z-P2A- 
                 1629 
                 5542 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Ig Fc 
                 CD8SP-CD16A-V158-ECD-v1-Myc-z-P2A- 
                 1630 
                 5543 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-2F2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1631 
                 5544 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-GA101-(vL-vH)-Myc-z-P2A- 
                 1632 
                 5545 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-Leu16-(vL-vH)-Myc-z-P2A- 
                 1633 
                 5546 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-11B8-(vL-vH)-Myc-z-P2A- 
                 1634 
                 5547 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-2C6-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1635 
                 5548 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-2H7-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1636 
                 5549 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-hA20-(vL-vH)-Myc-z-P2A- 
                 1637 
                 5550 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-BM-CA-1925-v4-(vL-vH)-Myc-z- 
                 1638 
                 5551 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-Ubli-v4-(vL-vH)-Myc-z-P2A- 
                 1639 
                 5552 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-2H7-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1640 
                 5553 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-hlF5-(vL-vH)-Myc-z-P2A- 
                 1641 
                 5554 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-7D8-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1642 
                 5555 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-AME-33-(vL-vH)-Myc-z-P2A- 
                 1643 
                 5556 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-h10F4v2-(vL-vH)-Myc-z-P2A- 
                 1644 
                 5557 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-H22Rhov2ACDRKA-(vL-vH)-Myc- 
                 1645 
                 5558 
               
               
                   
                 z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-m971-(vL-vH)-Myc-z-P2A- 
                 1646 
                 5559 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-m971-HL-(vH-vL)-Myc-z-P2A- 
                 1647 
                 5560 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD30 
                 CD8SP-CD30-5F11-(vL-vH)-Myc-z-P2A- 
                 1648 
                 5561 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD30 
                 CD8SP-CD30-Ac10-(vL-vH)-Myc-z-P2A- 
                 1649 
                 5562 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD32 
                 CD8SP-CD32-Med9-(vL-vH)-Myc-z-P2A- 
                 1650 
                 5563 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-AF5-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1651 
                 5564 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-huMyc9-(vL-vH)-Myc-z-P2A- 
                 1652 
                 5565 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-Boehr2800308-(vL-vH)-Myc-z- 
                 1653 
                 5566 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-Him3-4-(vL-vH)-Myc-z-P2A- 
                 1654 
                 5567 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-SGNh2H12-(vL-vH)-Myc-z-P2A- 
                 1655 
                 5568 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-15G15-33-(vL-vH)-Myc-z-P2A- 
                 1656 
                 5569 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-33H4-(vL-vH)-Myc-z-P2A- 
                 1657 
                 5570 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD33 
                 CD8SP-CD33-9C3-2-(vL-vH)-Myc-z-P2A- 
                 1658 
                 5571 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD34 
                 CD8SP-CD34-hu4C7-(vL-vH)-Myc-z-P2A- 
                 1659 
                 5572 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD44v6 
                 CD8SP-CD44v6-Biwa8-(vL-vH)-Myc-z-P2A- 
                 1660 
                 5573 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD70 
                 CD8SP-CD70-h1F6-(vL-vH)-Myc-z-P2A- 
                 1661 
                 5574 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD79b 
                 CD8SP-CD79b-2F2-(vL-vH)-Myc-z-P2A- 
                 1662 
                 5575 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD79b 
                 CD8SP-huMA79bv28-(vL-vH)-Myc-z-P2A- 
                 1663 
                 5576 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD99 
                 CD8SP-CD99-hu12E7-(vL-vH)-Myc-z-P2A- 
                 1664 
                 5577 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-CSL362-(vL-vH)-Myc-z-P2A- 
                 1665 
                 5578 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-1172-(vL-vH)-Myc-z-P2A- 
                 1666 
                 5579 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-DART-1-(vL-vH)-Myc-z-P2A- 
                 1667 
                 5580 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-DART-2-(vL-vH)-Myc-z-P2A- 
                 1668 
                 5581 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-I3RB18-(vL-vH)-Myc-z-P2A- 
                 1669 
                 5582 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-hu3E3-(vL-vH)-Myc-z-P2A- 
                 1670 
                 5583 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-9F6-(vL-vH)-Myc-z-P2A- 
                 1671 
                 5584 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-I3RB2-(vL-vH)-Myc-z-P2A- 
                 1672 
                 5585 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-1176-(vL-vH)-Myc-z-P2A- 
                 1673 
                 5586 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-Ritx2-CD123-8B11-(vL-vH)-Myc-z-P2A- 
                 1674 
                 5587 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-2B8-(vL-vH)-Myc-z-P2A- 
                 1675 
                 5588 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-9D7-(vL-vH)-Myc-z-P2A- 
                 1676 
                 5589 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD123 
                 CD8SP-CD123-3B10-(vL-vH)-Myc-z-P2A- 
                 1677 
                 5590 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD138 
                 CD8SP-CD138-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1678 
                 5591 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD179b 
                 CD8SP-CD179b-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1679 
                 5592 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD276 
                 CD8SP-CD276-17-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1680 
                 5593 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD324 
                 CD8SP-CD324-SC10-6-(vL-vH)-Myc-z-P2A- 
                 1681 
                 5594 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD324 
                 CD8SP-CD324-hSC10-17-(vL-vH)-Myc-z-P2A- 
                 1682 
                 5595 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CDH6 
                 CD8SP-CDH6-NOV710-(vL-vH)-Myc-z-P2A- 
                 1683 
                 5596 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CDH6 
                 CD8SP-CDH6-NOV712-(vL-vH)-Myc-z-P2A- 
                 1684 
                 5597 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CDH17 
                 CD8SP-CDH17-PTA001A4-(vL-vH)-Myc-z-P2A- 
                 1685 
                 5598 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CDH19 
                 CD8SP-CDH19-16A4-(vL-vH)-Myc-z-P2A- 
                 1686 
                 5599 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EGFR 
                 CD8SP-Cetuximab-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1687 
                 5600 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CLEC5A 
                 CD8SP-CLEC5A-8H8F5-(vL-vH)-Myc-z-P2A- 
                 1688 
                 5601 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CLEC5A 
                 CD8SP-CLEC5A-3E12A2-(vL-vH)-Myc-z-P2A- 
                 1689 
                 5602 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GR/LHR 
                 SP-CGHb-Linker-CGHa-Myc-z-P2A-hNEMO- 
                 1690 
                 5603 
               
               
                 (Gonadotropin 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Receptor) 
                   
                   
                   
               
               
                 CLL1 
                 CD8SP-CLL1-M26-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1691 
                 5604 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CLL1 
                 CD8SP-CLL1-M32-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1692 
                 5605 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CLL1 
                 CD8SP-CLL1-21C9-L2H3-(vL-vH)-Myc-z-P2A- 
                 1693 
                 5606 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CLL1 
                 CD8SP-CLL1-6E7L4H1e-(vL-vH)-Myc-z-P2A- 
                 1694 
                 5607 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CLL1 
                 CD8SP-CLL1-hu1075-v1-(vL-vH)-Myc-z-P2A- 
                 1695 
                 5608 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CLL1 
                 CD8SP-CLL1-hu1075-v2-(vL-vH)-Myc-z-P2A- 
                 1696 
                 5609 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CMVpp65/MHC 
                 CD8SP-CMVpp65-F5-(vL-vH)-Myc-z-P2A- 
                 1697 
                 5610 
               
               
                 class I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-huLuc63-(vL-vH)-Myc-z-P2A- 
                 1698 
                 5611 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-HuLuc64-(vL-vH)-Myc-z-P2A- 
                 1699 
                 5612 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-huLuc90-(vL-vH)-Myc-z-P2A- 
                 1700 
                 5613 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-PDL241-(vL-vH)-Myc-z-P2A- 
                 1701 
                 5614 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-Hu27A-(vL-vH)-Myc-z-P2A- 
                 1702 
                 5615 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-ScHu34C3-(vL-vH)-Myc-z-P2A- 
                 1703 
                 5616 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-Hu31-D2-(vL-vH)-Myc-z-P2A- 
                 1704 
                 5617 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1(SLAMF7) 
                 CD8SP-CS1-Luc34-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1705 
                 5618 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CS1 (SLAMF7) 
                 CD8SP-CS1-LucX2-(vL-vH)-Myc-z-P2A- 
                 1706 
                 5619 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CSF2RA 
                 CD8SP-CSF2RA-Ab6-(vL-vH)-Myc-z-P2A- 
                 1707 
                 5620 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CSF2RA 
                 CD8SP-CSF2RA-Ab1-(vL-vH)-Myc-z-P2A- 
                 1708 
                 5621 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CXCR4 and 
                 CD8SP-CXCR4-1-vHH-Linker-CD123-1-vHH- 
                 1709 
                 5622 
               
               
                 CD123 
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CXCR4 and 
                 CD8SP-CXCR4-2-VHH-Linker-CD123-2-VHH- 
                 1710 
                 5623 
               
               
                 CD123 
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 DLL3 (Delta Like 
                 CD8SP-DLL3-hSC16-13-(vL-vH)-Myc-z-P2A- 
                 1711 
                 5624 
               
               
                 Ligand 3) 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 DLL3 
                 CD8SP-DLL3-hSC16-56-(vL-vH)-Myc-z-P2A- 
                 1712 
                 5625 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EBNA3c/MHC 
                 CD8SP-EBNA3c-315-(vL-vH)-Myc-z-P2A- 
                 1713 
                 5626 
               
               
                 class I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EBV-gp350 
                 CD8SP-EBV-gp350-(vL-vH)-Myc-z-P2A- 
                 1714 
                 5627 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EGFR 
                 CD8SP-EGFR1-vHH-Myc-z-P2A-hNEMO- 
                 1715 
                 5628 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EGFR &amp; CEA 
                 CD8SP-EGFR1-vHH-Linker-CEA1-vHH-Myc-z- 
                 1716 
                 5629 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EGFR &amp; CEA 
                 CD8SP-EGFR33-vHH-Linker-CEA5-vHH-Myc-z- 
                 1717 
                 5630 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EGFRvIII 
                 CD8SP-EGFRvIII-139-(vL-vH)-Myc-z-P2A- 
                 1718 
                 5631 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EGFRvIII 
                 CD8SP-EGFRvIII-2173-(vL-vH)-Myc-z-P2A- 
                 1719 
                 5632 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EpCam1 
                 CD8SP-Epcam1-MM1-(vL-vH)-Myc-z-P2A- 
                 1720 
                 5633 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EpCam1 
                 CD8SP-Epcam1-D5K5-(vL-vH)-Myc-z-P2A- 
                 1721 
                 5634 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 FLT3 
                 CD8SP-FLT3-NC7-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1722 
                 5635 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 FITC 
                 CD8SP-FITC-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1723 
                 5636 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 FITC 
                 CD8SP-FITC-4M-53-(vL-vH)-Myc-z-P2A- 
                 1724 
                 5637 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 FITC 
                 CD8SP-FITC-E2-HL-(vH-vL)-Myc-z-P2A- 
                 1725 
                 5638 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Influenza A HA 
                 CD8SP-FLU-MEDI-8852-(vL-vH)-Myc-z-P2A- 
                 1726 
                 5639 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 FR1 (Folate 
                 CD8SP-FR1-huMov19-(vL-vH)-Myc-z-P2A- 
                 1727 
                 5640 
               
               
                 Receptor alpha) 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 FSHR (Fo11icle 
                 CD8SP-FSHb-Linker-CGHa-Myc-z-P2A-hNEMO- 
                 1728 
                 5641 
               
               
                 Stimulating 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Hormone 
                   
                   
                   
               
               
                 Receptor) 
                   
                   
                   
               
               
                 GAD (Glutamic 
                 CD8SP-GAD-G3H8-(vL-vH)-Myc-z-P2A- 
                 1729 
                 5642 
               
               
                 Acid Decarboxylase)/ 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MHC class I complex 
                   
                   
                   
               
               
                 GD2 
                 CD8SP-GD2-hu14-18-(vL-vH)-Myc-z-P2A- 
                 1730 
                 5643 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GD2 
                 CD8SP-GD2-hu3F8-(vL-vH)-Myc-z-P2A- 
                 1731 
                 5644 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GD3 
                 CD8SP-GD3-KM-641-(vL-vH)-Myc-z-P2A- 
                 1732 
                 5645 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GFRa4 (GDNF 
                 CD8SP-GFRAlpha4-P4-6-(vL-vH)-Myc-z-P2A- 
                 1733 
                 5646 
               
               
                 Family Receptor 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Alpha 4) 
                   
                   
                   
               
               
                 GFRa4 
                 CD8SP-GFRa4-P4-10-(vL-vH)-Myc-z-P2A- 
                 1734 
                 5647 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GM1 
                 CD8SP-GM1-5B2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1735 
                 5648 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GM1 
                 CD8SP-GM1-7E5-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1736 
                 5649 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GPRC5D (G- 
                 CD8SP-GPRC5D-ET150-5-(vL-vH)-Myc-z-P2A- 
                 1737 
                 5650 
               
               
                 protein coupled 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 receptor family C 
                   
                   
                   
               
               
                 group 5 member D) 
                   
                   
                   
               
               
                 GPRC5D 
                 CD8SP-GPRC5D-ET150-18-(vL-vH)-Myc-z-P2A- 
                 1738 
                 5651 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GPRC5D 
                 CD8SP-GPRC5D-ET150-1-(vL-vH)-Myc-z-P2A- 
                 1739 
                 5652 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GPRC5D 
                 CD8SP-GPRC5D-ET150-2-(vL-vH)-Myc-z-P2A- 
                 1740 
                 5653 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 gp100/MHC class I 
                 CD8SP-gp100-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1741 
                 5654 
               
               
                 complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 gp100/MHC class I 
                 CD8SP-gp100-G2D12-(vL-vH)-Myc-z-P2A- 
                 1742 
                 5655 
               
               
                 complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GPC3 (Glypican 3) 
                 CD8SP-GPC3-4E5-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1743 
                 5656 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 gpNMB 
                 CD8SP-gpNMB-115-(vL-vH)-Myc-z-P2A- 
                 1744 
                 5657 
               
               
                 (Glycoprotein 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Nmb) 
                   
                   
                   
               
               
                 GRP78 
                 CD8SP-GRP78-GC18-(vL-vH)-Myc-z-P2A- 
                 1745 
                 5658 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Her2 
                 CD8SP-Her2-5F7-vHH-Myc-z-P2A-hNEMO- 
                 1746 
                 5659 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Her2 
                 IgHSP-Her2-Affi-Myc-z-P2A-hNEMO-K277A- 
                 1747 
                 5660 
               
               
                   
                 Flag-T2A-PAC 
                   
                   
               
               
                 Her2 
                 CD8SP-Her2-1-Darpin-Myc-z-P2A-hNEMO- 
                 1748 
                 5661 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Her2 
                 IgHSP-Her2-2-Darpin-Myc-z-P2A-hNEMO- 
                 1749 
                 5662 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Her2 
                 CD8SP-Her2-5F7-vHH-Linker-Her2-47D5-vHH- 
                 1750 
                 5663 
               
               
                   
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Her2 
                 CD8SP-Her2-Hu4D5-(vL-vH)-Myc-z-P2A- 
                 1751 
                 5664 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Her3 
                 CD8SP-Her3-17B05So-vHH-Myc-z-P2A-hNEMO- 
                 1752 
                 5665 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Her3 
                 CD8SP-Her3-Affi-Myc-z-P2A-hNEMO-K277A- 
                 1753 
                 5666 
               
               
                   
                 Flag-T2A-PAC 
                   
                   
               
               
                 Her2 and Her3 
                 CD8SP-Her3-17B05So-vHH-Linker-Her2-2D3- 
                 1754 
                 5667 
               
               
                   
                 vHH-Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HIV1-gag/MHC 
                 CD8SP-HIV1-E5-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1755 
                 5668 
               
               
                 class I complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HIV1-envelop 
                 CD8SP-HIV1-3BNC117-(vL-vH)-Myc-z-P2A- 
                 1756 
                 5669 
               
               
                 glycoprotein 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HIV1-envelop 
                 CD8SP-HIV1-PGT-128-(vL-vH)-Myc-z-P2A- 
                 1757 
                 5670 
               
               
                 glycoprotein 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HIV1-envelop 
                 CD8SP-HIV1-VR-C01-(vL-vH)-Myc-z-P2A- 
                 1758 
                 5671 
               
               
                 glycoprotein 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HIV1-envelop 
                 CD8SP-HIV1-X5-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1759 
                 5672 
               
               
                 glycoprotein 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HLA-A2 
                 CD8SP-HLA-A2-3PB2-(vL-vH)-Myc-z-P2A- 
                 1760 
                 5673 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HMW-MAA 
                 CD8SP-HMW-MAA-hIND-(vL-vH)-Myc-z-P2A- 
                 1761 
                 5674 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HPV16-E7/MHC 
                 CD8SP-HPV16-7-8-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1762 
                 5675 
               
               
                 class I complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HPV16-E7/MHC 
                 CD8SP-HPV16-2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1763 
                 5676 
               
               
                 class I complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 HTLV1- 
                 CD8SP-HTLV-TAX-T3F2-(vL-vH)-Myc-z-P2A- 
                 1764 
                 5677 
               
               
                 TAX/MHC class I 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 complex 
                   
                   
                   
               
               
                 HTLV1- 
                 CD8SP-HTLV-TAX-T3E3-(vL-vH)-Myc-z-P2A- 
                 1765 
                 5678 
               
               
                 TAX/MHC class I 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 complex 
                   
                   
                   
               
               
                 IL11Ra 
                 CD8SP-IL11Ra-8E2-Ts107-(vL-vH)-Myc-z-P2A- 
                 1766 
                 5679 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 IL6Ra 
                 IgHSP-IL6R-304-vHH-Myc-z-P2A-hNEMO- 
                 1767 
                 5680 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 IL13Ra2 
                 CD8SP-IL13Ra2-hu107-(vL-vH)-Myc-z-P2A- 
                 1768 
                 5681 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 IL13Ra2 
                 CD8SP-IL13Ra2-Hu108-(vL-vH)-Myc-z-P2A- 
                 1769 
                 5682 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 KSHV-K8.1 
                 CD8SP-KSHV-4C3-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1770 
                 5683 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 LAMP1 
                 CD8SP-LAMP1-humab1-2-(vL-vH)-Myc-z-P2A- 
                 1771 
                 5684 
               
               
                 (Lysosomal- 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 associated 
                   
                   
                   
               
               
                 membrane 
                   
                   
                   
               
               
                 protein 1) 
                   
                   
                   
               
               
                 LAMP1 
                 CD8SP-LAMP1-Mb4-(vL-vH)-Myc-z-P2A- 
                 1772 
                 5685 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 LewisY 
                 CD8SP-LewisY-huS193-(vL-vH)-Myc-z-P2A- 
                 1773 
                 5686 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 L1CAM 
                 CD8SP-L1CAM-9-3-HU3-(vL-vH)-Myc-z-P2A- 
                 1774 
                 5687 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 LHR 
                 SP-LHb-Linker-CGHa-Myc-z-P2A-hNEMO- 
                 1775 
                 5688 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Lym1 
                 CD8SP-Lym1-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1776 
                 5689 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Lym2 
                 CD8SP-Lym2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1777 
                 5690 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD79b 
                 CD8SP-huMA79bv28-(vL-vH)-Myc-z-P2A- 
                 1778 
                 5691 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MART1/MHC 
                 CD8SP-MART1-CAG10-(vL-vH)-Myc-z-P2A- 
                 1779 
                 5692 
               
               
                 class I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MART1/MHC 
                 CD8SP-MART1-CLA12-(vL-vH)-Myc-z-P2A- 
                 1780 
                 5693 
               
               
                 class I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Mesothelin 
                 CD8SP-Mesothelin-m912-(vL-vH)-Myc-z-P2A- 
                 1781 
                 5694 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 cMet 
                 CD8SP-cMet-171-vHH-Myc-z-P2A-hNEMO- 
                 1782 
                 5695 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 cMet and Her3 
                 CD8SP-cMET-171-vHH-Linker-Her3-21F06-vHH- 
                 1783 
                 5696 
               
               
                   
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-175-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1784 
                 5697 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-161-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1785 
                 5698 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-161-HL-(vH-vL)-Myc-z-P2A- 
                 1786 
                 5699 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-2-MPL-111-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1787 
                 5700 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-178-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1788 
                 5701 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-AB317-(vL-vH)-Myc-z-P2A- 
                 1789 
                 5702 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-12E10-(vL-vH)-Myc-z-P2A- 
                 1790 
                 5703 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-huVB22Bw5-(vL-vH)-Myc-z-P2A- 
                 1791 
                 5704 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Muc1/MHC class I 
                 CD8SP-Muc1-D6-M3B8-(vL-vH)-Myc-z-P2A- 
                 1792 
                 5705 
               
               
                 complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Muc1/MHC class I 
                 CD8SP-MUCl-D6-M3Al-(vL-vH)-Myc-z-P2A- 
                 1793 
                 5706 
               
               
                 complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Muc16 
                 CD8SP-Muc 16-4H11-(vL-vH)-Myc-z-P2A- 
                 1794 
                 5707 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 EGFR 
                 CD8SP-Nimotuzumab-(vL-vH)-Myc-z-P2A- 
                 1795 
                 5708 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 NKG2D Ligand 
                 CD8SP-NKG2D-(GGGGS-GGGGD)-Myc-z-P2A- 
                 1796 
                 5709 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 NKG2D 
                 CD8SP-NKG2D-MS-(vL-vH)-Myc-z-P2A- 
                 1797 
                 5710 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 NY-BR1 
                 CD8SP-NYBR1-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1798 
                 5711 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 NY-ESO/MHC 
                 CD8SP-NYESO-T1-(vL-vH)-Myc-z-P2A- 
                 1799 
                 5712 
               
               
                 class I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 NY-ESO/MHC 
                 CD8SP-NYESO-T1-(vL-vH)-Myc-z-P2A- 
                 1800 
                 5713 
               
               
                 class I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PD1 ligand (e.g., 
                 CD8SP-PD1-ECD-Myc-z-P2A-hNEMO-K277A- 
                 1801 
                 5714 
               
               
                 PDL1) 
                 Flag-T2A-PAC 
                   
                   
               
               
                 PDL1 
                 CD8SP-PDL1-Atezoli-(vL-vH)-Myc-z-P2A- 
                 1802 
                 5715 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PDL1 
                 CD8SP-PDL1-SP142-(vL-vH)-Myc-z-P2A- 
                 1803 
                 5716 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PDL1 
                 CD8SP-PDL1-10A5-(vL-vH)-Myc-z-P2A- 
                 1804 
                 5717 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PSCA (Prostate 
                 CD8SP-PSCA-Ha14-121-(vL-vH)-Myc-z-P2A- 
                 1805 
                 5718 
               
               
                 stem cell antigen) 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PSCA (Prostate 
                 CD8SP-PSCA-Ha14-117-(vL-vH)-Myc-z-P2A- 
                 1806 
                 5719 
               
               
                 stem cell antigen) 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PR1/MHC class I 
                 CD8SP-PR1-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1807 
                 5720 
               
               
                 complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PSMA (Prostate 
                 CD8SP-PSMA-006-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1808 
                 5721 
               
               
                 Specific Membrane 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Antigen) 
                   
                   
                   
               
               
                 PSMA 
                 CD8SP-PSMA-J591-(vL-vH)-Myc-z-P2A- 
                 1809 
                 5722 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PTK7 (Tyrosine- 
                 CD8SP-PTK7-hSC6-23-(vL-vH)-Myc-z-P2A- 
                 1810 
                 5723 
               
               
                 protein kinase-like 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 7) 
                   
                   
                   
               
               
                 PTK7 
                 CD8SP-PTK7-SC6-10-2-(vL-vH)-Myc-z-P2A- 
                 1811 
                 5724 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 ROR1 
                 CD8SP-ROR1-4A5-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1812 
                 5725 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 ROR1 
                 CD8SP-ROR1-4C10-(vL-vH)-Myc-z-P2A- 
                 1813 
                 5726 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Mesothelin 
                 CD8SP-SD1-vHH-Linker-SD2-vHH-Myc-z-P2A- 
                 1814 
                 5727 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 SLea 
                 CD8SP-SLea-7E3-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1815 
                 5728 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 SLea 
                 CD8SP-SLea-5B1-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1816 
                 5729 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 SSEA4 (stage- 
                 CD8SP-SSEA4-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1817 
                 5730 
               
               
                 specific embryonic 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 antigen 4) 
                   
                   
                   
               
               
                 TCRB1 (TCR beta 
                 CD8SP-TCRB1-CPO1-E09-(vL-vH)-Myc-z-P2A- 
                 1818 
                 5731 
               
               
                 1 constant chain) 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TCRB1 
                 CD8SP-TCRB1-Jovi1-(vL-vH)-Myc-z-P2A- 
                 1819 
                 5732 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TCRB2 (TCRbeta 
                 CD8SP-TCRB2-CP01-D05-(vL-vH)-Myc-z-P2A- 
                 1820 
                 5733 
               
               
                 2 constant chain) 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TCRB2 
                 CD8SP-TCRB2-CP01-E05-(vL-vH)-Myc-z-P2A- 
                 1821 
                 5734 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TCRgd (TCR 
                 CD8SP-TCRgd-G5-4-(vL-vH)-Myc-z-P2A- 
                 1822 
                 5735 
               
               
                 gamma/delta) 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 hTERT/MHC class 
                 CD8SP-TERT-4A9-T540-(vL-vH)-Myc-z-P2A- 
                 1823 
                 5736 
               
               
                 I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 hTERT/MHC class 
                 CD8SP-TERT-3G3-T865-(vL-vH)-Myc-z-P2A- 
                 1824 
                 5737 
               
               
                 I complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Tissue Factor-1 
                 CD8SP-TGFBR2-Ab1-(vL-vH)-Myc-z-P2A- 
                 1825 
                 5738 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TGFBR2 
                 CD8SP-TF1-98-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1826 
                 5739 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TIM1/HAVCR 
                 CD8SP-TIM1-HVCR1-270-2-(vL-vH)-Myc-z- 
                 1827 
                 5740 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TIM1/HAVCR 
                 CD8SP-TIM1-HVCR1-ARD5-(vL-vH)-Myc-z- 
                 1828 
                 5741 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TnAg 
                 CD8SP-TnAg-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1829 
                 5742 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Tn-Muc1 
                 CD8SP-TnMuc1-hu5E5-RHA8-RKA-2-(vL-vH)- 
                 1830 
                 5743 
               
               
                   
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-hTPO-Myc-z-P2A-hNEMO-K277A-Flag- 
                 1831 
                 5744 
               
               
                   
                 T2A-PAC 
                   
                   
               
               
                 TROP2 
                 CD8SP-TROP2-ARA47-HV3KV3-(vL-vH)-Myc- 
                 1832 
                 5745 
               
               
                 (Trophoblast cell- 
                 z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 surface antigen-2) 
                   
                   
                   
               
               
                 TROP2 
                 CD8SP-TROP2-h7E6-SVG-(vL-vH)-Myc-z-P2A- 
                 1833 
                 5746 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TSHR 
                 SP-TSHb-Linker-CGHa-Myc-z-P2A-hNEMO- 
                 1834 
                 5747 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TSHR 
                 CD8SP-TSHR-K1-70-(vL-vH)-Myc-z-P2A- 
                 1835 
                 5748 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TSHR 
                 CD8SP-TSHR-KB1-(vL-vH)-Myc-z-P2A- 
                 1836 
                 5749 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TSHR 
                 CD8SP-TSHR-5C9-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1837 
                 5750 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 TSLPR (thymic 
                 CD8SP-TSLPR-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1838 
                 5751 
               
               
                 stromal 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 lymphopoietin 
                   
                   
                   
               
               
                 receptor) 
                   
                   
                   
               
               
                 Tyrosinase/MHC 
                 CD8SP-Tyros-B2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1839 
                 5752 
               
               
                 class I complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Tyrosinase/MHC 
                 CD8SP-Tyros-MC1-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1840 
                 5753 
               
               
                 class I complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Tyrosinase/MHC 
                 CD8SP-Tyros-TA2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1841 
                 5754 
               
               
                 class I complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 VEGFR3 
                 CD8SP-VEGFR3-Ab1-(vL-vH)-Myc-z-P2A- 
                 1842 
                 5755 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 WT1/MHC class I 
                 CD8SP-WT1-Ab1-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1843 
                 5756 
               
               
                 complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 WT1/MHC class I 
                 CD8SP-WT1-Ab5-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1844 
                 5757 
               
               
                 complex 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 WT1/MHC class I 
                 CD8SP-MYC3-WT1-Ab13-(vL-vH)-Myc-z-P2A- 
                 1845 
                 5758 
               
               
                 complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 WT1/MHC class I 
                 CD8SP-MYC3-WT1-Ab15-(vL-vH)-Myc-z-P2A- 
                 1846 
                 5759 
               
               
                 complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CDH19 
                 CD8SP-CDH19-4B10-(vL-vH)-Myc-z-P2A- 
                 1847 
                 5760 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Folate Receptor 
                 CD8SP-FRbeta-m923-(vL-vH)-Myc-z-P2A- 
                 1848 
                 5761 
               
               
                 beta 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 LHR (Luteinizing 
                 CD8SP-LHR-8B7-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1849 
                 5762 
               
               
                 hormone Receptor) 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 LHR 
                 CD8SP-LHR-5F4-21-(vL-vH)-Myc-z-P2A- 
                 1850 
                 5763 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 B7H4 
                 CD8SP-B7H4-hu22C10-(vL-vH)-Myc-z-P2A- 
                 1851 
                 5764 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 B7H4 
                 CD8SP-B7H4-hu1D11-(vL-vH)-Myc-z-P2A- 
                 1852 
                 5765 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 IgE 
                 CD8SP-IgE-omalizumab-(vL-vH)-Myc-z-P2A- 
                 1853 
                 5766 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD23 
                 CD8SP-CD23-p5E8-(vL-vH)-Myc-z-P2A- 
                 1854 
                 5767 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GCC (Guanylyl 
                 CD8SP-GCC-5F9-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1855 
                 5768 
               
               
                 cyclase C) 
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 GCC 
                 CD8SP-GCC-Ab229-(vL-vH)-Myc-z-P2A- 
                 1856 
                 5769 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD200R 
                 CD8SP-CD200R-huDx182-(vL-vH)-Myc-z-P2A- 
                 1857 
                 5770 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Tn-Muc1 
                 CD8SP-Tn-Muc1-5E5-HL-(vH-vL)-Myc-z-P2A- 
                 1858 
                 5771 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-5-HL-(vH-vL)-Myc-z-P2A- 
                 1859 
                 5772 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-10-HL-(vH-vL)-Myc-z-P2A- 
                 1860 
                 5773 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-31-HL-(vH-vL)-Myc-z-P2A- 
                 1861 
                 5774 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-53-HL-(vH-vL)-Myc-z-P2A- 
                 1862 
                 5775 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD22 
                 CD8SP-CD22-65-HL-(vH-vL)-Myc-z-P2A- 
                 1863 
                 5776 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Tn-Muc1 
                 CD8SP-Tn-Muc1-5E5-(vH-vL)-Myc-z-P2A- 
                 1864 
                 5777 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Kappa Light Chain 
                 CD8SP-Kappa-LC1-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1865 
                 5778 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PTK7 
                 CD8SP-PTK7-7C8-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1866 
                 5779 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 PTK7 
                 CD8SP-PTK7-12C6a-(vL-vH)-Myc-z-P2A- 
                 1867 
                 5780 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-hCD19-EUK5-13-(vL-vH)-Myc-z-P2A- 
                 1868 
                 5781 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Ras 
                 CD8SP-Ras-Ab2-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1869 
                 5782 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Ras 
                 CD8SP-Ras-Ab4-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1870 
                 5783 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Claudin 18.2 
                 CD8SP-CLD18A2-43A11-(vL-vH)-Myc-z-P2A- 
                 1871 
                 5784 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Claudin 18.2 
                 CD8SP-CLD18A2-175D10-(vL-vH)-Myc-z-P2A- 
                 1872 
                 5785 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD43 
                 CD8SP-CD43-huJL-1-257-10-(vL-vH)-Myc-z- 
                 1873 
                 5786 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD69L 
                 CD8SP-CD69L-DREG200-(vL-vH)-Myc-z-P2A- 
                 1874 
                 5787 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 NY-ESO-1/MHC I 
                 CD8SP-NYESO-35-15-(vL-vH)-Myc-z-P2A- 
                 1875 
                 5788 
               
               
                 complex 
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Pgp 
                 CD8SP-Pgp-9F11-(vH-vL)-Myc-z-P2A-hNEMO- 
                 1876 
                 5789 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Streptag 
                 CD8SP-Streptag-(vL-vH)-Myc-z-P2A-hNEMO- 
                 1877 
                 5790 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-Hu-161-2-(vL-vH)-Myc-z-P2A- 
                 1878 
                 5791 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 Pgp 
                 CD8SP-Pgp-MRK16-(vL-vH)-Myc-z-P2A- 
                 1879 
                 5792 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-353-vHH-Myc-z-P2A-hNEMO- 
                 1880 
                 5793 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-917-vHH-Myc-z-P2A-hNEMO- 
                 1881 
                 5794 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-353-vHH-Linker-BCMA917-vHH- 
                 1882 
                 5795 
               
               
                   
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD38 
                 CD8SP-CD38-717-vHH-Myc-z-P2A-hNEMO- 
                 1883 
                 5796 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-346-vHH-Myc-z-P2A-hNEMO- 
                 1884 
                 5797 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD38-BCMA 
                 CD8SP-CD38-717-vHH-Ecoil-BCMA-346-vHH- 
                 1885 
                 5798 
               
               
                   
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-348-vHH-Myc-z-P2A-hNEMO- 
                 1886 
                 5799 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD38 
                 CD8SP-CD3 8-331-vHH-Myc-z-P2A-hNEMO- 
                 1887 
                 5800 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA-CD38 
                 CD8SP-BCMA-vHH-348-Ecoil-CD38-331-vHH- 
                 1888 
                 5801 
               
               
                   
                 Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-vHH-Myc-z-P2A-hNEMO-K277A- 
                 1889 
                 5802 
               
               
                   
                 Flag-T2A-PAC 
                   
                   
               
               
                 CD20 
                 CD8SP-CD20-vHH-Myc-z-P2A-hNEMO-K277A- 
                 1890 
                 5803 
               
               
                   
                 Flag-T2A-PAC 
                   
                   
               
               
                 CD19 
                 CD8SP-CD19-vHH-Linker-CD20-vHH-Myc-z- 
                 1891 
                 5804 
               
               
                   
                 P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-948-vHH-Myc-z-P2A-hNEMO- 
                 1892 
                 5805 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-972-vHH-Myc-z-P2A-hNEMO- 
                 1893 
                 5806 
               
               
                   
                 K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-948-vHH-PG4SP-BCMA-972- 
                 1894 
                 5807 
               
               
                   
                 vHH-Myc-z-P2A-hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 BCMA 
                 CD8SP-BCMA-948-vHH-PG4SP-BCMA-972- 
                 1895 
                 5808 
               
               
                   
                 vHH-Ecoilx4-Myc-z-P2A-hNEMO-K277A-Flag- 
                   
                   
               
               
                   
                 T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-hu-175-2-(vL-vH)-Myc-z-P2A- 
                 1896 
                 5809 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 MPL 
                 CD8SP-MPL-hu-111-2-(vL-vH)-Myc-z-P2A- 
                 1897 
                 5810 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD179a 
                 CD8SP-CD179a-2460-B04-(vL-vH)-Myc-z-P2A- 
                 1898 
                 5811 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
                   
                   
               
               
                 CD179a 
                 CD8SP-CD179a-2462-E07-(vL-vH)-Myc-z-P2A- 
                 1899 
                 5812 
               
               
                   
                 hNEMO-K277A-Flag-T2A-PAC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 SEQ ID IDENTIFICATION OF CARS/BITES USING ANTIGEN BINDING DOMAINS 
               
               
                 DESCRIBED FOR zCAR-NEMO-K277A (TABLE 12) AS A TEMPLATE 
               
            
           
           
               
               
               
               
            
               
                   
                 EXEMPLARY 
                   
                   
               
               
                 CAR 
                 CAR/Bispecific T cell 
               
               
                 ARCHITECTURE 
                 Engager 
                 SEQ ID NO DNA 
                 SEQ ID NO PRT 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 zCAR- 
                 CD8SP-FMC63-(vL-vH)- 
                 1594-1857 
                 1858-1899 
                 5507-5770 
                 5771-5812 
               
               
                 NEMO- 
                 Myc-z-P2A-hNEMO-K277A- 
               
               
                 K277A 
                 Flag-T2A-PAC 
               
               
                 zCAR-K13 
                 CD8SP-FMC63-(vL-vH)- 
                 1016-1285 
                   
                 4929-5192 
               
               
                   
                 Myc-z-P2A-K13-Flag-T2A- 
               
               
                   
                 PAC 
               
               
                 BBz CAR 
                 CD8SP-FMC63-(vL-vH)- 
                 1318-1581 
                   
                 5231-5494 
               
               
                   
                 Myc-BBz-T2A-PAC 
               
               
                 CD3ε-TFP- 
                 CD8SP-FMC63-(vL-vH)- 
                 1900-2163 
                 2164-2205 
                 5813-6076 
                 6077-6118 
               
               
                 NEMO- 
                 CD3e-ECDTMCP-opt2-P2A- 
               
               
                 K277A 
                 hNEMO-K277A-Flag-T2A- 
               
               
                   
                 PAC 
               
               
                 CD3δ-TFP- 
                 CD8SP-FMC63-(vL-vH)- 
                 2206-2469 
                 2470-2511 
                 6119-6382 
                 6383-6424 
               
               
                 NEMO- 
                 CD3d-ECDTMCP-opt2-P2A- 
               
               
                 K277A 
                 hNEMO-K277A-Flag-T2A- 
               
               
                   
                 PAC 
               
               
                 CDγ-TFP- 
                 CD8SP-FMC63-(vL-vH)- 
                 2512-2775 
                 2776-2817 
                 6425-6688 
                 6689-6730 
               
               
                 NEMO- 
                 CD3z-ECDTMCP-opt2-P2A- 
               
               
                 K277A 
                 hNEMO-K277A-Flag-T2A- 
               
               
                   
                 PAC 
               
               
                 CDζ-TFP- 
                 CD8SP-FMC63-(vL-vH)- 
                 2818-3081 
                 3082-3123 
                 6731-6994 
                 6995-7036 
               
               
                 NEMO- 
                 CD3z-ECDTMCP-opt2-P2A- 
               
               
                 K277A 
                 hNEMO-K277A-Flag-T2A- 
               
               
                   
                 PAC 
               
               
                 Bispecific T 
                 CD8SP-FMC63-scFv-Linker- 
                 3545-3814 
                   
                 7458-7721 
               
               
                 cell Engager 
                 CD3-scFv-Myc-His 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 14 
               
             
            
               
                   
               
               
                 Ab-TCR CONSTRUCTS WITH DIFFERENT ANTIGEN BINDING DOMAINS. 
               
            
           
           
               
               
               
               
            
               
                   
                 Name of CAR constructs including the name of 
                 SEQ ID NO 
                 SEQ ID NO 
               
               
                 Target 
                 antigen binding domain 
                 (DNA) 
                 (PRT) 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 CD19 
                 CD8SP-FMC63-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3124 
                 7037 
               
               
                   
                 SP-FMC63-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD19 
                 CD8SP-huFMC63-11-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3125 
                 7038 
               
               
                   
                 P2A-SP-huFMC63-11-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD19 
                 CD8SP-CD19Bu12-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3126 
                 7039 
               
               
                   
                 P2A-SP-CD19Bu12-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD19 
                 CD8SP2-CD19MM-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3127 
                 7040 
               
               
                   
                 P2A-SP-CD19MM-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD19 
                 CD8SP-CD19-4G7-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3128 
                 7041 
               
               
                   
                 P2A-SP-CD19-4G7-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 HIV1-env 
                 CD8SP-HIV1-N6-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3129 
                 7042 
               
               
                   
                 P2A-SP-HIV1-N6-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 ALK 
                 CD8SP-Alk-48-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3130 
                 7043 
               
               
                   
                 SP-Alk-48-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 ALK 
                 CD8SP-Alk-58-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3131 
                 7044 
               
               
                   
                 SP-Alk-5 8-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 Amyloid 
                 SP-Amyloid-158-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3132 
                 7045 
               
               
                   
                 SP-Amyloid-158-vH-[IgG1-CH1-TCRa-SDVP-6MD]- 
               
               
                   
                 F-F2A-hNEMO-K277A 
               
               
                 Biotin 
                 CD8SP-dc-Avidin-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3133 
                 7046 
               
               
                   
                 SP-dc-Avidin-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 CD45 
                 CD8SP-BC8-CD45-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3134 
                 7047 
               
               
                   
                 P2A-SP-BC8-CD45-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 BCMA 
                 CD8SP-BCMA-J6M0-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3135 
                 7048 
               
               
                   
                 P2A-SP-BCMA-J6M0-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 BCMA 
                 CD8SP-BCMA-huC12A3-L3H3-vL-[IgCL-TCRb- 
                 3136 
                 7049 
               
               
                   
                 IAH-6MD]-F-P2A-SP-BCMA-huC12A3-L3H3-vH- 
               
               
                   
                 [IgG1-CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO- 
               
               
                   
                 K277A 
               
               
                 BCMA 
                 CD8SP-BCMA-ET-40-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3137 
                 7050 
               
               
                   
                 P2A-SP-BCMA-ET-40-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 BCMA 
                 CD8SP-BCMA-ET-54-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3138 
                 7051 
               
               
                   
                 P2A-SP-BCMA-ET-54-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CCR4 
                 CD8SP-CCR4-humAb1567-vL-[IgCL-TCRb-IAH- 
                 3139 
                 7052 
               
               
                   
                 6MD]-F-P2A-SP-CCR4-humAb1567-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 HIV1-env 
                 CD8SP-CD4-ECD-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3140 
                 7053 
               
               
                   
                 SP-DC-SIGN-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 CD5 
                 CD8SP-CD5-9-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3141 
                 7054 
               
               
                   
                 SP-CD5-9-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD5 
                 CD8SP-CD5-18-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3142 
                 7055 
               
               
                   
                 SP-CD5-18-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 IgFc 
                 CD8SP-CD16A-V158-ECD-v1-[IgCL-TCRb-IAH- 
                 3143 
                 7056 
               
               
                   
                 6MD]-P2A-CD8SP2-CD16A-V158-ECD-v2-[IgG1- 
               
               
                   
                 CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 IgFc 
                 CD8SP-CD16A-V158-ECD-v1-[IgCL-TCRb-IAH- 
                 3144 
                 7057 
               
               
                   
                 6MD]-P2A-SP-CD123-1-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD20 
                 CD8SP-CD20-2F2-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3145 
                 7058 
               
               
                   
                 P2A-SP-CD20-2F2-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD20 
                 CD8SP-CD20-GA101-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3146 
                 7059 
               
               
                   
                 P2A-SP-CD20-GA101-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD22 
                 CD8SP-CD22-h10F4v2-vL-[IgCL-TCRb-IAH-6MD]- 
                 3147 
                 7060 
               
               
                   
                 F-P2A-SP-CD22-h10F4v2-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD22 
                 CD8SP-CD22-H22Rhov2ACDRKA-vL-[IgCL-TCRb- 
                 3148 
                 7061 
               
               
                   
                 IAH-6MD]-F-P2A-SP-CD22-H22Rhov2ACDRKA- 
               
               
                   
                 vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO- 
               
               
                   
                 K277A 
               
               
                 CD22 
                 CD8SP-CD22-m971-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3149 
                 7062 
               
               
                   
                 P2A-SP-CD22-m971-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD30 
                 CD8SP-CD30-5F11-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3150 
                 7063 
               
               
                   
                 P2A-SP-CD30-5F11-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD30 
                 CD8SP-CD30-Ac10-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3151 
                 7064 
               
               
                   
                 P2A-SP-CD30-Ac10-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD32 
                 CD8SP-CD32-Med9-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3152 
                 7065 
               
               
                   
                 P2A-SP-CD32-Med9-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD33 
                 CD8SP-CD33-AF5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3153 
                 7066 
               
               
                   
                 P2A-SP-CD33-AF5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD33 
                 CD8SP-CD33-huMyc9-vL-[IgCL-TCRb-IAH-6MD]- 
                 3154 
                 7067 
               
               
                   
                 F-P2A-SP-CD33-huMyc9-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD34 
                 CD8SP-CD34-hu4C7-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3155 
                 7068 
               
               
                   
                 P2A-SP-CD34-hu4C7-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD44v6 
                 CD8SP-CD44v6-Biwa8-vL-[IgCL-TCRb-IAH-6MD]- 
                 3156 
                 7069 
               
               
                   
                 F-P2A-SP-CD44v6-Biwa8-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD70 
                 CD8SP-CD70-h1F6-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3157 
                 7070 
               
               
                   
                 P2A-SP-CD70-h1F6-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD79b 
                 CD8SP-CD79b-2F2-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3158 
                 7071 
               
               
                   
                 P2A-SP-CD79b-2F2-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD123 
                 CD8SP-CD123-CSL362-vL-[IgCL-TCRb-IAH-6MD]- 
                 3159 
                 7072 
               
               
                   
                 F-P2A-SP-CD123-CSL362-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD138 
                 CD8SP-CD138-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3160 
                 7073 
               
               
                   
                 SP-CD138-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD179b 
                 CD8SP-CD179b-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3161 
                 7074 
               
               
                   
                 SP-CD179b-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD276 
                 CD8SP-CD276-17-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3162 
                 7075 
               
               
                   
                 P2A-SP-CD276-17-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD324 
                 CD8SP-CD324-SC10-6-vL-[IgCL-TCRb-IAH-6MD]- 
                 3163 
                 7076 
               
               
                   
                 F-P2A-SP-CD324-SC10-6-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD324 
                 CD8SP-CD324-hSC10-17-vL-[IgCL-TCRb-IAH- 
                 3164 
                 7077 
               
               
                   
                 6MD]-F-P2A-SP-CD324-hSC10-17-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CDH6 
                 CD8SP-CDH6-NOV710-vL-[IgCL-TCRb-IAH-6MD]- 
                 3165 
                 7078 
               
               
                   
                 F-P2A-SP-CDH6-NOV710-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CDH6 
                 CD8SP-CDH6-NOV712-vL-[IgCL-TCRb-IAH-6MD]- 
                 3166 
                 7079 
               
               
                   
                 F-P2A-SP-CDH6-NOV712-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CDH17 
                 CD8SP-CDH17-PTA001A4-vL-[IgCL-TCRb-IAH- 
                 3167 
                 7080 
               
               
                   
                 6MD]-F-P2A-SP-CDH17-PTA001A4-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CDH19 
                 CD8SP-CDH19-16A4-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3168 
                 7081 
               
               
                   
                 P2A-SP-CDH19-16A4-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 EGFR 
                 CD8SP-Cetuximab-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3169 
                 7082 
               
               
                   
                 P2A-SP-Cetuximab-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CLEC5A 
                 CD8SP-CLEC5A-8H8F5-vL-[IgCL-TCRb-IAH- 
                 3170 
                 7083 
               
               
                   
                 6MD]-F-P2A-SP-CLEC5A-8H8F5-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CLEC5A 
                 CD8SP-CLEC5A-3E12A2-vL-[IgCL-TCRb-IAH- 
                 3171 
                 7084 
               
               
                   
                 6MD]-F-P2A-SP-CLEC5A-3E12A2-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 GR/LHR 
                 SP-CGHb-[IgCL-TCRb-IAH-6MD]-F-P2A-SP-CGHa- 
                 3172 
                 7085 
               
               
                   
                 [IgG1-CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO- 
               
               
                   
                 K277A 
               
               
                 CLL1 
                 CD8SP-CLL1-M26-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3173 
                 7086 
               
               
                   
                 P2A-SP-CLL1-M26-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CLL1 
                 CD8SP-CLL1-M32-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3174 
                 7087 
               
               
                   
                 P2A-SP-CLL1-M32-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CMVpp65 
                 CD8SP-CMVpp65-F5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3175 
                 7088 
               
               
                   
                 P2A-SP-CMVpp65-F5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CS1 
                 CD8SP-CS1-huLuc63-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3176 
                 7089 
               
               
                   
                 P2A-SP-huLuc63-vH-[IgG1-CH1-TCRa-SDVP-6MD]- 
               
               
                   
                 F-F2A-hNEMO-K277A 
               
               
                 CS1 
                 CD8SP-HuLuc64-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3177 
                 7090 
               
               
                   
                 SP-HuLuc64-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CS1 
                 CD8SP-CS1-huLuc90-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3178 
                 7091 
               
               
                   
                 P2A-SP-huLuc90-vH-[IgG1-CH1-TCRa-SDVP-6MD]- 
               
               
                   
                 F-F2A-hNEMO-K277A 
               
               
                 CSF2RA 
                 CD8SP-CSF2RA-Ab6-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3179 
                 7092 
               
               
                   
                 P2A-SP-CSF2RA-Ab6-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CSF2RA 
                 CD8SP-CSF2RA-Ab1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3180 
                 7093 
               
               
                   
                 P2A-SP-CSF2RA-Ab1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD123 
                 IgHSP-CD123-2-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3181 
                 7094 
               
               
                   
                 P2A-SP-CD123-1-vHH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD123 &amp; 
                 IgHSP-CD123-2-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3182 
                 7095 
               
               
                 IgFc 
                 P2A-CD8SP1-CD16A-V158-ECD-v1-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD123 &amp; 
                 IgHSP-CD123-2-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3183 
                 7096 
               
               
                 IgFc 
                 P2A-CD8SP2-CD16A-V158-ECD-v2-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD123 &amp; 
                 IgHSP-CD123-2-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3184 
                 7097 
               
               
                 MPL 
                 P2A-CD8SP-MPL-161-HL-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CXCR4 &amp; 
                 CD8SP-CXCR4-1-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3185 
                 7098 
               
               
                 CD123 
                 P2A-SP-CD123-1-vHH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CXCR4 &amp; 
                 CD8SP-CXCR4-2-VHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3186 
                 7099 
               
               
                 CD123 
                 P2A-SP-CD123-2-VHH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 DLL3 
                 CD8SP-DLL3-hSC16-13-vL-[IgCL-TCRb-IAH- 
                 3187 
                 7100 
               
               
                   
                 6MD]-F-P2A-SP-DLL3-hSC16-13-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 DLL3 
                 CD8SP-DLL3-hSC16-56-vL-[IgCL-TCRb-IAH- 
                 3188 
                 7101 
               
               
                   
                 6MD]-F-P2A-SP-DLL3-hSC16-56-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 EBNA3c 
                 CD8SP-EBNA3c-315-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3189 
                 7102 
               
               
                   
                 P2A-SP-EBNA3c-315-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 EBV- 
                 CD8SP-EBV-gp350-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3190 
                 7103 
               
               
                 gp350 
                 P2A-SP-EBV-gp3 50-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 EGFR 
                 CD8SP-EGFR1-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3191 
                 7104 
               
               
                   
                 P2A-SP-CEA1-vHH-[IgG1-CH1-TCRa-SDVP-6MD]- 
               
               
                   
                 F-F2A-hNEMO-K277A 
               
               
                 EGFR 
                 CD8SP-EGFR33-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3192 
                 7105 
               
               
                   
                 P2A-SP-CEA5-vHH-[IgG1-CH1-TCRa-SDVP-6MD]- 
               
               
                   
                 F-F2A-hNEMO-K277A 
               
               
                 EGFRvIII 
                 CD8SP-EGFRvIII-139-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3193 
                 7106 
               
               
                   
                 P2A-SP-EGFRvIII-139-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 EGFRvIII 
                 CD8SP-EGFRvIII-2173-vH-[IgCL-TCRb-IAH-6MD]- 
                 3194 
                 7107 
               
               
                   
                 F-P2A-SP-EGFRvIII-2173-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 EpCam1 
                 CD8SP-Epcam1-MM1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3195 
                 7108 
               
               
                   
                 P2A-SP-Epcam1-MM1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 EpCam1 
                 CD8SP-Epcam1-D5K5-vL-[IgCL-TCRb-IAH-6MD]- 
                 3196 
                 7109 
               
               
                   
                 F-P2A-SP-Epcam1-D5K5-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 FLT3 
                 CD8SP-FLT3-NC7-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3197 
                 7110 
               
               
                   
                 P2A-SP-FLT3-NC7-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 FITC 
                 CD8SP-FITC-vL-[IgCL-TCRb-IAH-6MD]-F-P2A-SP- 
                 3198 
                 7111 
               
               
                   
                 FITC-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 Influenza 
                 CD8SP-FLU-MEDI-8852-vL-[IgCL-TCRb-IAH- 
                 3199 
                 7112 
               
               
                 A HA 
                 6MD]-F-P2A-SP-FLU-MEDI-8852-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 Folate 
                 CD8SP-FR1-huMov19-vL-[IgCL-TCRb-IAH-6MD]- 
                 3200 
                 7113 
               
               
                 Receptor 1 
                 F-P2A-SP-FR1-huMov19-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 FSHR 
                 CD8SP-FSHb-vL-[IgCL-TCRb-IAH-6MD]-F-P2A-SP- 
                 3201 
                 7114 
               
               
                   
                 CGHa-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 GD2 
                 CD8SP-GD2-hu14-18-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3202 
                 7115 
               
               
                   
                 P2A-SP-GD2-hu14-18-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GD2 
                 CD8SP-GD2-hu3F8-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3203 
                 7116 
               
               
                   
                 P2A-SP-GD2-hu3F8-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GD3 
                 CD8SP-GD3-KM-641-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3204 
                 7117 
               
               
                   
                 P2A-SP-GD3-KM-641-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GFRa4 
                 CD8SP-GFRAlpha4-P4-6-vL-[IgCL-TCRb-IAH- 
                 3205 
                 7118 
               
               
                   
                 6MD]-F-P2A-SP-GFRAlpha4-P4-6-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 GFRa4 
                 CD8SP-GFRa4-P4-10-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3206 
                 7119 
               
               
                   
                 P2A-SP-GFRa4-P4-10-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 FUCOSYL- 
                 CD8SP-GM1-5B2-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3207 
                 7120 
               
               
                 GM1 
                 P2A-SP-GM1-5B2-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 FUCOSYL- 
                 CD8SP-GM1-7E5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3208 
                 7121 
               
               
                 GM1 
                 P2A-SP-GM1-7E5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GPRC5D 
                 CD8SP-GPRC5D-ET150-5-vL-[IgCL-TCRb-IAH- 
                 3209 
                 7122 
               
               
                   
                 6MD]-F-P2A-SP-GPRC5D-ET150-5-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 GPRC5D 
                 CD8SP-GPRC5D-ET150-18-vL-[IgCL-TCRb-IAH- 
                 3210 
                 7123 
               
               
                   
                 6MD]-F-P2A-SP-GPRC5D-ET150-18-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 gp100 
                 CD8SP-gp100-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3211 
                 7124 
               
               
                   
                 SP-gp100-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 gp100 
                 CD8SP-gp100-G2D12-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3212 
                 7125 
               
               
                   
                 P2A-SP-gp100-G2D12-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GPC3 
                 CD8SP-GPC3-4E5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3213 
                 7126 
               
               
                   
                 P2A-SP-GPC3-4E5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 gpNMB 
                 CD8SP-gpNMB-115-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3214 
                 7127 
               
               
                   
                 P2A-SP-gpNMB-115-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GRP78 
                 CD8SP-GRP78-GC18-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3215 
                 7128 
               
               
                   
                 P2A-SP-GRP78-GC18-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Her2 
                 CD8SP-Her2-1-Darpin-[IgCL-TCRb-IAH-6MD]-F- 
                 3216 
                 7129 
               
               
                   
                 P2A-SP-Her2-2-Darpin-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Her2 
                 CD8SP-Her2-5F7-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3217 
                 7130 
               
               
                   
                 P2A-SP-Her2-47D5-vHH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Her2 
                 CD8SP-Her2-Hu4D5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3218 
                 7131 
               
               
                   
                 P2A-SP-Her2-Hu4D5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Her2 &amp; 
                 CD8SP-Her3-17B05So-vHH-[IgCL-TCRb-IAH- 
                 3219 
                 7132 
               
               
                 Her3 
                 6MD]-F-P2A-SP-Her2-2D3-vHH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 HIV1-gag 
                 CD8SP-HIV1-E5-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3220 
                 7133 
               
               
                   
                 SP-HIV1-E5-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 HIV1-env 
                 CD8SP-HIV1-3BNC117-vL-[IgCL-TCRb-IAH-6MD]- 
                 3221 
                 7134 
               
               
                   
                 F-P2A-SP-HIV1-3BNC117-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 HIV1-env 
                 CD8SP-HIV1-PGT-128-vL-[IgCL-TCRb-IAH-6MD]- 
                 3222 
                 7135 
               
               
                   
                 F-P2A-SP-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 HIV1-env 
                 CD8SP-HIV1-VR-C01-vL-[IgCL-TCRb-IAH-6MD]- 
                 3223 
                 7136 
               
               
                   
                 F-P2A-SP-HIV1-VR-C01-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 HIV1-env 
                 CD8SP-HIV1-X5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3224 
                 7137 
               
               
                   
                 P2A-SP-HIV1-X5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 HMW- 
                 CD8SP-HMW-MAA-hIND-vL-[IgCL-TCRb-IAH- 
                 3225 
                 7138 
               
               
                 MAA 
                 6MD]-F-P2A-SP-HMW-MAA-hIND-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 HTLV1- 
                 CD8SP-HTLV-TAX-T3F2-vL-[IgCL-TCRb-IAH- 
                 3226 
                 7139 
               
               
                 TAX 
                 6MD]-F-P2A-SP-TAX-T3F2-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 HTLV1- 
                 CD8SP-HTLV-TAX-T3E3-vL-[IgCL-TCRb-IAH- 
                 3227 
                 7140 
               
               
                 TAX 
                 6MD]-F-P2A-SP-TAX-T3E3-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 IL11Ra 
                 CD8SP-IL11Ra-8E2-Ts107-vL-[IgCL-TCRb-IAH- 
                 3228 
                 7141 
               
               
                   
                 6MD]-F-P2A-SP-IL11Ra-8E2-Ts107-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 IL6Ra &amp; 
                 IgHSP-IL6R-304-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3229 
                 7142 
               
               
                 CD19 
                 P2A-SP-FMC63-scFV-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 IL13Ra2 
                 CD8SP-IL13Ra2-hu107-vL-[IgCL-TCRb-IAH-6MD]- 
                 3230 
                 7143 
               
               
                   
                 F-P2A-SP-IL13Ra2-hu107vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 IL13Ra2 
                 CD8SP-IL13Ra2-Hu108-vL-[IgCL-TCRb-IAH-6MD]- 
                 3231 
                 7144 
               
               
                   
                 F-P2A-SP-IL13Ra2-Hu108-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 KSHV- 
                 CD8SP-KSHV-4C3-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3232 
                 7145 
               
               
                 K8.1 
                 P2A-SP-4C3-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 LAMP1 
                 CD8SP-LAMP1-humab1-2-vL-[IgCL-TCRb-IAH- 
                 3233 
                 7146 
               
               
                   
                 6MD]-F-P2A-SP-LAMP1-humab1-2vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 LAMP1 
                 CD8SP-LAMP1-Mb4-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3234 
                 7147 
               
               
                   
                 P2A-SP-LAMP1-Mb4-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 LewisY 
                 CD8SP-LewisY-huS193-vL-[IgCL-TCRb-IAH-6MD]- 
                 3235 
                 7148 
               
               
                   
                 F-P2A-SP-LewisY-huS193-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 L1CAM 
                 CD8SP-L1CAM-9-3-HU3-vL-[IgCL-TCRb-IAH- 
                 3236 
                 7149 
               
               
                   
                 6MD]-F-P2A-SP-L1CAM-9-3-HU3-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 LHR 
                 SP-LHb-[IgCL-TCRb-IAH-6MD]-F-P2A-SP-CGHa- 
                 3237 
                 7150 
               
               
                   
                 [IgG1-CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO- 
               
               
                   
                 K277A 
               
               
                 Lym1 
                 CD8SP-Lym1-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3238 
                 7151 
               
               
                   
                 SP-Lym1-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 Lym2 
                 CD8SP-Lym2-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3239 
                 7152 
               
               
                   
                 SP-Lym2-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 CD79b 
                 CD8SP-huMA79bv28-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3240 
                 7153 
               
               
                   
                 P2A-SP-huMA79bv28-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 MART1 
                 CD8SP-MART1-CAG10-vL-[IgCL-TCRb-IAH- 
                 3241 
                 7154 
               
               
                   
                 6MD]-F-P2A-SP-MART1-CAG10-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 MART1 
                 CD8SP-MART1-CLA12-vL-[IgCL-TCRb-IAH-6MD]- 
                 3242 
                 7155 
               
               
                   
                 F-P2A-SP-MART1-CLA12-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 Mesothelin 
                 CD8SP-Mesothelin-m912-vL-[IgCL-TCRb-IAH- 
                 3243 
                 7156 
               
               
                   
                 6MD]-F-P2A-SP-m912-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 cMet 
                 CD8SP-cMET-171-vHH-[IgCL-TCRb-IAH-6MD]-F- 
                 3244 
                 7157 
               
               
                   
                 P2A-SP-Her3-21F06-vHH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 MPL 
                 CD8SP-MPL-175-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3245 
                 7158 
               
               
                   
                 P2A-SP-175-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 MPL 
                 CD8SP-MPL-161-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3246 
                 7159 
               
               
                   
                 P2A-SP-161-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 MPL 
                 CD8SP2-MPL-111-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3247 
                 7160 
               
               
                   
                 P2A-SP-MPL-111-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 MPL 
                 CD8SP-MPL-178-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3248 
                 7161 
               
               
                   
                 P2A-SP-178-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 MPL 
                 CD8SP-MPL-AB317-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3249 
                 7162 
               
               
                   
                 P2A-SP-AB317-vH-[IgG1-CH1-TCRa-SDVP-6MD]- 
               
               
                   
                 F-F2A-hNEMO-K277A 
               
               
                 MPL 
                 CD8SP-MPL-12E10-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3250 
                 7163 
               
               
                   
                 P2A-SP-12E10-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 MPL 
                 CD8SP-MPL-huVB22Bw5-vL-[IgCL-TCRb-IAH- 
                 3251 
                 7164 
               
               
                   
                 6MD]-F-P2A-SP-MPL-huVB22Bw5-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 Muc1 
                 CD8SP-Muc1-D6-M3B8-vL-[IgCL-TCRb-IAH-6MD]- 
                 3252 
                 7165 
               
               
                   
                 F-P2A-SP-Muc1-D6-M3B8-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 Muc1 
                 CD8SP-MUC1-D6-M3A1-vL-[IgCL-TCRb-IAH- 
                 3253 
                 7166 
               
               
                   
                 6MD]-F-P2A-SP-MUC1-D6-M3A1-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 Muc16 
                 CD8SP-Muc16-4H11-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3254 
                 7167 
               
               
                   
                 P2A-SP-Muc16-4H11-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 EGFR 
                 CD8SP-Nimotuzumab-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3255 
                 7168 
               
               
                   
                 P2A-SP-Nimotuzumab-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 NKG2D 
                 CD8SP-NKG2D-(G4SG4D)-[IgCL-TCRb-IAH-6MD]- 
                 3256 
                 7169 
               
               
                   
                 F-P2A-SP-NKG2D-(G4SG4D)-v2-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 NKG2D 
                 CD8SP-NKG2D-MS-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3257 
                 7170 
               
               
                   
                 P2A-SP-NKG2D-MS-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 NYBR1 
                 CD8SP-NYBR1-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3258 
                 7171 
               
               
                   
                 SP-NYBR1-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 NY-ESO 
                 CD8SP-NYESO-T1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3259 
                 7172 
               
               
                   
                 P2A-SP-NYESO-T1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 NY-ESO 
                 CD8SP-NYESO-T1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3260 
                 7173 
               
               
                   
                 P2A-SP-NYESO-T2-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 PD1 
                 SP-PD1-ECD-[IgCL-TCRb-IAH-6MD]-P2A-SP-PD1- 
                 3261 
                 7174 
               
               
                 Ligand 
                 opt-ECD-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 PDL1 
                 CD8SP-PDL1-Atezoli-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3262 
                 7175 
               
               
                   
                 P2A-SP-PDL1-Atezoli-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 PDL1 
                 CD8SP-PDL1-SP142-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3263 
                 7176 
               
               
                   
                 P2A-SP-PDL1-SP142-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 PDL1 
                 CD8SP-PDL1-10A5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3264 
                 7177 
               
               
                   
                 P2A-SP-PDL1-10A5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 PSCA 
                 CD8SP-PSCA-Ha14-121-vL-[IgCL-TCRb-IAH- 
                 3265 
                 7178 
               
               
                   
                 6MD]-F-P2A-SP-P SCA-Ha14-121-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 PSCA 
                 CD8SP-PSCA-Ha14-117-vL-[IgCL-TCRb-IAH- 
                 3266 
                 7179 
               
               
                   
                 6MD]-F-P2A-SP-P SCA-Ha14-117-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 PR1 
                 CD8SP-PR1-vL-[IgCL-TCRb-IAH-6MD]-F-P2A-SP- 
                 3267 
                 7180 
               
               
                   
                 PR1-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 PSMA 
                 CD8SP-PSMA-006-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3268 
                 7181 
               
               
                   
                 P2A-SP-PSMA-006-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 PSMA 
                 CD8SP-PSMA-J591-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3269 
                 7182 
               
               
                   
                 P2A-SP-PSMA-J591-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 PTK7 
                 CD8SP-PTK7-hSC6-23-vL-[IgCL-TCRb-IAH-6MD]- 
                 3270 
                 7183 
               
               
                   
                 F-P2A-SP-PTK7-hSC6-23-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 PTK7 
                 CD8SP-PTK7-SC6-10-2-vL-[IgCL-TCRb-IAH-6MD]- 
                 3271 
                 7184 
               
               
                   
                 F-P2A-SP-PTK7-SC6-10-2-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 ROR1 
                 CD8SP-ROR1-4A5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3272 
                 7185 
               
               
                   
                 P2A-SP-ROR1-4A5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 ROR1 
                 CD8SP-ROR1-4C10-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3273 
                 7186 
               
               
                   
                 P2A-SP-ROR1-4C10-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Mesothelin 
                 CD8SP-SD1-[IgCL-TCRb-IAH-6MD]-F-P2A-SP- 
                 3274 
                 7187 
               
               
                   
                 SD2-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO- 
               
               
                   
                 K277A 
               
               
                 SLea 
                 CD8SP-SLea-7E3-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3275 
                 7188 
               
               
                   
                 P2A-SP-SLea-7E3-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 SLea 
                 CD8SP-SLea-5B1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3276 
                 7189 
               
               
                   
                 P2A-SP-SLea-5B1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 SSEA4 
                 CD8SP-SSEA4-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3277 
                 7190 
               
               
                   
                 SP-SSEA4-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 Tyrosinase 
                 CD8SP-TA2-vL-[IgCL-TCRb-IAH-6MD]-F-P2A-SP- 
                 3278 
                 7191 
               
               
                   
                 TA2-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 TCRB1 
                 CD8SP-TCRB1-CP01-E09-vL-[IgCL-TCRb-IAH- 
                 3279 
                 7192 
               
               
                   
                 6MD]-F-P2A-SP-TCRB1-CP01-E09-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 TCRB1 
                 CD8SP-TCRB1-Jovi1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3280 
                 7193 
               
               
                   
                 P2A-SP-TCRB1-Jovi1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 TCRB2 
                 CD8SP-TCRB2-CP01-D05-vL-[IgCL-TCRb-IAH- 
                 3281 
                 7194 
               
               
                   
                 6MD]-F-P2A-SP-TCRB2-CP01-D05-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 TCRB2 
                 CD8SP-TCRB2-CP01-E05-vL-[IgCL-TCRb-IAH- 
                 3282 
                 7195 
               
               
                   
                 6MD]-F-P2A-SP-TCRB2-CP01-E05-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 TCRgd 
                 CD8SP-TCRgd-G5-4-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3283 
                 7196 
               
               
                   
                 P2A-SP-TCRgd-G5-4-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 hTERT 
                 CD8SP-TERT-4A9-T540-vL-[IgCL-TCRb-IAH- 
                 3284 
                 7197 
               
               
                   
                 6MD]-F-P2A-SP-TERT-4A9-T540-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 hTERT 
                 CD8SP-TERT-3G3-T865-vL-[IgCL-TCRb-IAH- 
                 3285 
                 7198 
               
               
                   
                 6MD]-F-P2A-SP-TERT-3G3-T865-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 TGFBR2 
                 CD8SP-TGFBR2-Ab1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3286 
                 7199 
               
               
                   
                 P2A-SP-TGFBR2-Ab1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 TIM1 
                 CD8SP-TIM1-HVCR1-270-2-vL-[IgCL-TCRb-IAH- 
                 3287 
                 7200 
               
               
                   
                 6MD]-F-P2A-SP-TIM1-HVCR1-270-2-vH-[IgG1- 
               
               
                   
                 CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 TIM1 
                 CD8SP-TIM1-HVCR1-ARD5-vL-[IgCL-TCRb-IAH- 
                 3288 
                 7201 
               
               
                   
                 6MD]-F-P2A-SP-TIM1-HVCR1-ARD5vH-[IgG1- 
               
               
                   
                 CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 TnAg 
                 CD8SP-TnAg-vL-[IgCL-TCRb-IAH-6MD]-F-P2A-SP- 
                 3289 
                 7202 
               
               
                   
                 TnAg-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 Tn-Muc1 
                 CD8SP-TnMuc1-hu5E5-RHA8-RKA-2-vL-[IgCL- 
                 3290 
                 7203 
               
               
                   
                 TCRb-IAH-6MD]-F-P2A-SP-TnMuc1-hu5E5-RHA8- 
               
               
                   
                 RKA-2vH-[IgG1-CH1-TCRa-SDVP-6MD]-F-F2A- 
               
               
                   
                 hNEMO-K277A 
               
               
                 TROP2 
                 CD8SP-TROP2-ARA47-HV3KV3-vL-[IgCL-TCRb- 
                 3291 
                 7204 
               
               
                   
                 IAH-6MD]-F-P2A-SP-TROP2-ARA47-HV3KV3-vH- 
               
               
                   
                 [IgG1-CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO- 
               
               
                   
                 K277A 
               
               
                 TROP2 
                 CD8SP-TROP2-h7E6-SVG-vL-[IgCL-TCRb-IAH- 
                 3292 
                 7205 
               
               
                   
                 6MD]-F-P2A-SP-TROP2-h7E6-S VG-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 TSHR 
                 SP-TSHb-[IgCL-TCRb-IAH-6MD]-F-P2A-SP-CGHa- 
                 3293 
                 7206 
               
               
                   
                 [IgG1-CH1-TCRa-SDVP-6MD]-F-F2A-hNEMO- 
               
               
                   
                 K277A 
               
               
                 TSHR 
                 CD8SP-TSHR-K1-70-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3294 
                 7207 
               
               
                   
                 P2A-SP-TSHR-K1-70-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 TSHR 
                 CD8SP-TSHR-KB1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3295 
                 7208 
               
               
                   
                 P2A-SP-TSHR-KB1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 TSHR 
                 CD8SP-TSHR-5C9-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3296 
                 7209 
               
               
                   
                 P2A-SP-TSHR-5C9-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 TSLPR 
                 CD8SP-TSLPR-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3297 
                 7210 
               
               
                   
                 SP-TSLPR-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 Tyrosinase 
                 CD8SP-Tyros-B2-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3298 
                 7211 
               
               
                   
                 P2A-SP-Tyros-B2-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Tyrosinase 
                 CD8SP-Tyros-MC1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3299 
                 7212 
               
               
                   
                 P2A-SP-Tyros-MC1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Tyrosinase 
                 CD8SP-Tyrosinase-B2-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3300 
                 7213 
               
               
                   
                 P2A-SP-Tyrosinase-B2-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 VEGFR3 
                 CD8SP-VEGFR3-Ab1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3301 
                 7214 
               
               
                   
                 P2A-SP-VEGFR3-Ab1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 WT1 
                 CD8SP-WT1-Ab1-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3302 
                 7215 
               
               
                   
                 P2A-SP-WT1-Ab1-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 WT1 
                 CD8SP-WT1-Ab5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3303 
                 7216 
               
               
                   
                 P2A-SP-WT1-Ab5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 WT1 
                 CD8SP-MYC3-WT1-Ab13-vL-[IgCL-TCRb-IAH- 
                 3304 
                 7217 
               
               
                   
                 6MD]-F-P2A-SP-WT1-Ab13-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 WT1 
                 CD8SP-MYC3-WT1-Ab15-vL-[IgCL-TCRb-IAH- 
                 3305 
                 7218 
               
               
                   
                 6MD]-F-P2A-SP-WT1-Ab15-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD123 
                 CD8SP-CD123-1172-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3306 
                 7219 
               
               
                   
                 P2A-SP-CD123-1172-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CDH19 
                 CD8SP-CDH19-4B10-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3307 
                 7220 
               
               
                   
                 P2A-SP-CDH19-4B10-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 Folate 
                 CD8SP-FRbeta-m923-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3308 
                 7221 
               
               
                 Receptor 
                 P2A-SP-FRbeta-m923-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                 beta 
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 LHR 
                 CD8SP-LHR-8B7-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3309 
                 7222 
               
               
                   
                 P2A-SP-LHR-8B7-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 LHR 
                 CD8SP-LHR-5F4-21-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3310 
                 7223 
               
               
                   
                 P2A-SP-LHR-5F4-21-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 B7H4 
                 CD8SP-B7H4-hu22C10-vL-[IgCL-TCRb-IAH-6MD]- 
                 3311 
                 7224 
               
               
                   
                 F-P2A-SP-B7H4-hu22C10-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 B7H4 
                 CD8SP-B7H4-hu1D11-vL-[IgCL-TCRb-IAH-6MD]- 
                 3312 
                 7225 
               
               
                   
                 F-P2A-SP-B7H4-hu1D11-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 IgE 
                 CD8SP-IgE-omalizumab-vL-[IgCL-TCRb-IAH-6MD]- 
                 3313 
                 7226 
               
               
                   
                 F-P2A-SP-IgE-omalizumab-vH-[IgG1-CH1-TCRa- 
               
               
                   
                 SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD23 
                 CD8SP-CD23-p5E8-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3314 
                 7227 
               
               
                   
                 P2A-SP-CD23-p5E8-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GCC 
                 CD8SP-GCC-5F9-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3315 
                 7228 
               
               
                   
                 P2A-SP-GCC-5F9-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 GCC 
                 CD8SP-GCC-Ab229-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3316 
                 7229 
               
               
                   
                 P2A-SP-GCC-Ab229-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD200R 
                 CD8SP-CD200R-huDx182-vL-[IgCL-TCRb-IAH- 
                 3317 
                 7230 
               
               
                   
                 6MD]-F-P2A-SP-CD200R-huDx182-vH-[IgG1-CH1- 
               
               
                   
                 TCRa-SDVP-6MD]-F-F2A-hNEMO-K277A 
               
               
                 Tn-Muc1 
                 CD8SP-Tn-Muc1-5E5-vL-[IgCL-TCRb-IAH-6MD]-F- 
                 3318 
                 7231 
               
               
                   
                 P2A-SP-Tn-Muc1-5E5-vH-[IgG1-CH1-TCRa-SDVP- 
               
               
                   
                 6MD]-F-F2A-hNEMO-K277A 
               
               
                 CD22 
                 CD8SP-CD22-5-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3319 
                 7232 
               
               
                   
                 SP-CD22-5-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD22 
                 CD8SP-CD22-10-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3320 
                 7233 
               
               
                   
                 SP-CD22-10-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD22 
                 CD8SP-CD22-31-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3321 
                 7234 
               
               
                   
                 SP-CD22-31-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD22 
                 CD8SP-CD22-53-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3322 
                 7235 
               
               
                   
                 SP-CD22-53-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                 CD22 
                 CD8SP-CD22-65-vL-[IgCL-TCRb-IAH-6MD]-F-P2A- 
                 3323 
                 7236 
               
               
                   
                 SP-CD22-65-vH-[IgG1-CH1-TCRa-SDVP-6MD]-F- 
               
               
                   
                 F2A-hNEMO-K277A 
               
               
                   
               
            
           
         
       
     
     In some embodiments, the compositions comprise nucleic acids encoding conventional CARs 1-6 (Table 1), wherein the antigen specific domain of the CAR targets one or more specific antigens as described in Tables 6A-C or Tables 5-6 in PCT/US2017/064379, which are incorporated herein by reference. In some embodiments, the compositions comprise nucleic acids encoding any one or more of backbones 1-72 (Table 2) where the antigen specific domain of the encoded CAR targets one or more specific antigens as described in in Tables 6A-C or Tables 5-6 in PCT/US2017/064379. In some embodiments, the compositions comprise nucleic acids encoding backbone-1, wherein the antigen specific domain of the CAR in backbone-1 targets one or more cancer specific antigens as described herein an in Tables 6A-C or Tables 5-6 of PCT/US2017/064379. In some embodiments, the compositions comprise nucleic acids encoding backbone-1, wherein the antigen specific domain of the CAR in backbone-2 targets one or more cancer specific antigens as described herein an in Tables 6A-C or Tables 5-6 of PCT/US2017/064379. In some embodiments, the compositions comprise nucleic acids encoding backbone-1, wherein the antigen specific domain of the CAR in backbone-37 targets one or more cancer specific antigens as described herein an in Tables 6A-C or Tables 5-6 of PCT/US2017/064379. In some embodiments, the compositions comprise nucleic acids encoding backbone-1, wherein the antigen specific domain of the CAR in backbone-38 targets one or more cancer specific antigens as described herein an in Tables 6A-C or Tables 5-6 of PCT/US2017/064379. In some embodiments, the compositions comprise nucleic acids encoding backbone-1, wherein the antigen specific domain of the CAR in backbone-49 targets one or more cancer specific antigens as described herein an in Tables 6A-C or Tables 5-6 of PCT/US2017/064379. In some embodiments, the compositions comprise nucleic acids encoding backbone-1, wherein the antigen specific domain of the CAR in backbone-50 targets one or more cancer specific antigens as described herein an in Tables 6A-C or Tables 5-6 of PCT/US2017/064379. 
     In various embodiments, the isolated nucleic acid molecules encoding the non-naturally occurring immune receptor, e.g, a CAR, components of the backbones described herein, encode one, two, three or more antigen specific domains. For example, one or more ASD that binds specifically to a cancer associated antigen as described herein can be used. 
     The sequences of the ASD are contiguous with and in the same reading frame as a nucleic acid sequence encoding the remainder of the one or more chains of CAR. 
     In one embodiment, each antigen specific region comprises the full-length IgG heavy chain (specific for the target antigen) having the V H , CHL hinge, and the CH2 and CH3 (Fc) Ig domains, if the V H  domain alone is sufficient to confer antigen-specificity (“single-domain antibodies”). The full length IgG heavy chain may be linked to a co-stimulatory domain and an optional intracellular signaling domain via the appropriate transmembrane domain. If both, the V H  and the V L  domains, are necessary to generate a fully active antigen-specific targeting region, the VH-containing non-naturally occurring immune receptor, e.g, a CAR, and the full-length lambda light chain (IgL) are both introduced into the cells to generate an active antigen-specific targeting region. 
     In some embodiments, the antigen specific domain of the encoded non-naturally occurring immune receptor, e.g, a CAR, molecule comprises an antibody, an antibody fragment, an scFv, a Fv, a Fab, a (Fab′)2, a single domain antibody (SDAB), a vH or vL domain, or a camelid vHH domain. In some embodiments, the antigen binding domain of the non-naturally occurring immune receptor, e.g, a CAR, is a scFv antibody fragment that is humanized compared to the murine sequence of the scFv from which it is derived. 
     In some instances, scFvs can be prepared according to methods known in the art (for example, Bird et al., (1988) Science 242:423-426 and Huston et al., (1988) Proc.Natl. Acad. Sci. USA 85:5879-5883). ScFv molecules can be produced by linking V H  and VL regions together using flexible polypeptide linkers. The scFv molecules comprise a linker (e.g., a Ser-Gly linker) with an optimized length and/or amino acid composition (e.g., to optimize folding etc.). An scFv can comprise a linker of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more amino acid residues between its V L  and V H  regions. In some embodiments, the linker sequence comprises amino acids glycine and serine. In another embodiment, the linker sequence comprises sets of glycine and serine repeats. Variation in the linker length may retain or enhance activity, giving rise to superior efficacy in activity studies. In some embodiments, the antigen specific scFv antibody fragments are functional in that they bind the same antigen with the same or comparable affinity as the IgG antibody from which it is derived. In other embodiments, the antibody fragment has a lower binding affinity to the antigen compared to the antibody from which it is derived but is functional in that it provides a biological response described herein. In one embodiment, the CAR molecule comprises an antibody fragment that has a binding affinity K D  of 10 −4  M to 10 −8 M, 10 −5  M to 10 −7  M, 10 −6  M or 10 −8  M, for the target antigen. 
     In one embodiment, the antigen specific domain comprises one, two or all three heavy chain (hc) CDRs, hcCDR1, hcCDR2 and hcCDR3 of an antibody or a scFv listed herein (Table 6B; SEQ ID NOs: 14122-15039), and/or one, two or all three light chain (lc) CDRs, lcCDR1, lcCDR2 and lcCDR3 of an antibody or a scFv listed herein (Tables 6A; SEQ ID NOs: 13204-14121) (also also see, Tables 5-6 of PCT/US2017/064379). In some embodiments, the ASD comprises a V L  (or vL) fragment comprising all three light chain CDRs belonging to a specific scFv (Tables 6A; SEQ ID NOs: 13204-14121) or a V H  (or vH) fragment comprising all three heavy chain CDRs belonging to a specific scFv (Table 6B; SEQ ID NOs: 14122-15039) (see also, Tables 5-6 of PCT/US2017/064379). Table 6C provides the names, target antigens and SEQ ID Nos of the different scFvs whose vL and vL fragments and CDRs are listed in Tables 6A and 6B. The vL and vH fragments and the corresponding scFvs can be used in various embodiments of the disclosure to constructs the CARs described herein. 
     In another embodiment, the antigen specific domain comprises a humanized antibody or an antibody fragment. In some aspects, a non-human antibody is humanized, where specific sequences or regions of the antibody are modified to increase similarity to an antibody naturally produced in a human or fragment thereof. In one aspect, the antigen binding domain is humanized. A humanized antibody can be produced using a variety of techniques known in the art, including but not limited to, CDR-grafting, veneering or resurfacing, and chain shuffling. 
     In a further embodiment, each antigen specific domain of the non-naturally occurring immune receptor, e.g, a CAR, may comprise a divalent (or bivalent) single-chain variable fragment (di-scFvs, bi-scFvs). In, for example, CARs comprising di-scFVs, two scFvs specific for each antigen are linked together by producing a single peptide chain with two V H  and two V L  regions, yielding tandem scFvs. (Xiong, Cheng-Yi; Natarajan, A; Shi, XB; Denardo, GL; Denardo, SJ (2006). “Development of tumor targeting anti-MUC-1 multimer: effects of di-scFv unpaired cysteine location on PEGylation and tumor binding”. Protein Engineering Design and Selection 19 (8): 359-367; Kufer, Peter; Lutterbüse, Ralf; Baeuerle, Patrick A. (2004). “A revival of bispecific antibodies”. Trends in Biotechnology 22 (5): 238-244). CARs comprising at least two antigen-specific targeting regions would express two scFvs specific for each of the two antigens. The resulting ASD is joined to the co-stimulatory domain and the intracellular signaling domain via a hinge region and a transmembrane domain. Alternatively, non-naturally occurring immune receptor, e.g, a CAR, comprising two antigen specific targeting regions would express two vHH specific for each of the two antigens or two epitopes of the same antigen. Exemplary CARs targeting two antigens are represented by SEQ ID NOs: 1307 and 1310. 
     In another embodiment, each ASD of the non-naturally occurring immune receptor, e.g, a CAR, comprises a diabody. In a diabody, the scFvs are created with linker peptides that are too short for the two variable regions to fold together, driving the scFvs to dimerize. Still shorter linkers (one or two amino acids) lead to the formation of trimers, the so-called triabodies or tribodies. Tetrabodies may also be used. 
     In some embodiments, the ASD of the non-naturally occurring immune receptor, e.g, a CAR, comprises V HH  fragments (nanobodies) as described herein (see, Tables 5-6 of PCT/US2017/064379). In some embodiments, the ASD of the non-naturally occurring immune receptor, e.g, a CAR, comprises affibodies as described herein (see, Tables 5-6 of PCT/US2017/064379). 
     In another embodiment, the antigen specific binding domain comprises a ligand for a cognate expressed on a target cell. 
     In one embodiment, an antigen specific domain of a non-naturally occurring immune receptor, e.g, a CAR, against a target antigen is an antigen binding portion, e.g., CDRs, of vHH fragments targeting this antigen (see, Tables 5-6 of PCT/US2017/064379). 
     In one embodiment, an antigen specific domain of a non-naturally occurring immune receptor, e.g, a CAR, against a target antigen is an antigen binding portion of a non-immunoglobulin scaffold targeting this antigen (see, Tables 5-6 of PCT/US2017/064379). 
     In one embodiment, an antigen specific domain of a non-naturally occurring immune receptor, e.g, a CAR, against a target antigen is an antigen binding portion of a receptor known to bind this target antigen (see, Tables 5-6 of PCT/US2017/064379). 
     In another aspect, the antigen binding domain is a T cell receptor (“TCR”), or a fragment thereof, for example, a single chain TCR (scTCR). Methods to make such TCRs are known in the art. See, e.g., Willemsen RA et al, Gene Therapy 7: 1369-1377 (2000); Zhang T et al, Cancer Gene Ther 11: 487-496 (2004); Aggen et al, Gene Ther. 19(4):365-74 (2012) (references are incorporated herein by its entirety). For example, scTCR can be engineered that contain the Va and vβ genes from a T cell clone linked by a linker (e.g., a flexible peptide). This approach is very useful to cancer associated target that itself is intracellular, however, a fragment of such antigen (peptide) is presented on the surface of the cancer cells by MHC. 
     In some embodiments, the antigen specific domain is a T cell receptor specific for the target antigen or a fragment of the T cell receptor, wherein the fragment retains the specificity for the target antigen. 
     In some embodiments, antigen specific domain of a non-naturally occurring immune receptor, e.g, a CAR, described herein binds to a MHC presented peptide. Normally, peptides derived from endogenous proteins fill the pockets of Major histocompatibility complex (MHC) class I molecules, and are recognized by T cell receptors (TCRs) on CD8+ T lymphocytes. The MHC class I complexes are constitutively expressed by all nucleated cells. In cancer, virus-specific and/or tumor-specific peptide/MHC complexes represent a unique class of cell surface targets for immunotherapy. TCR-like antibodies targeting peptides derived from viral or tumor antigens in the context of human leukocyte antigen (HLA)-A1 or HLA-A2 have been described (see, e.g., Sastry et al., J Viral. 2011 85(5):1935-1942; Sergeeva et al., Blood, 2011117(16):4262-4272; Verma et al., Jlmmuno12010 184(4):2156-2165; Willemsen et al., Gene Ther20018(21) :1601-1608; Dao et al., Sci Transl Med 2013 5(176) :176ra33; Tassev et al., Cancer Gene Ther 2012 19(2):84-100). For example, TCR-like antibody can be identified from screening a library, such as a human scFv phage displayed library. Exemplary CARs that are based on TCR-like antibodies targeting WT1 in association with HLA-A2 are represented by SEQ ID NO: 1266 to SEQ ID NO: 1268. In the instant invention, CARs were generated using antigen binding domain derived from TCR like antibodies against several HLA-A2 restricted intracellular peptides. The target protein antigens, the peptide fragment and the sequence of the peptide are shown in Table 8. 
     In some embodiments, the antigens specific for disease which may be targeted by the non-naturally occurring immune receptor, e.g, a CAR, when expressed alone or with the accessory modules as described herein include but are not limited to any one or more of CDS; CD19; CD123; CD22; CD30; CD171; CS1 (also referred to as CD2 subset 1, CRACC, MPL, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TNF receptor family member B cell maturation (BCMass.); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMass.); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); Fms Like Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha (FRa or FR1); Folate receptor beta (FRb); Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CA1X); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDG1cp(1-1)Cer); transglutaminase 5 (TGSS); high molecular weight-melanoma associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; survivin; telomerase; prostate carcinoma tumor antigen-1 (PCT A-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P4501B 1 (CYP1B 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAXS); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation Endproducts (RAGE-1); renal ubiquitous 1 (RU1); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRD; Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRLS); and immunoglobulin lambda-like polypeptide 1 (IGLLl), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBR1, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen); Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL11Rα, IL13Ra2, CD179b-IGL11, TCRgamma-delta, NKG2D, CD32 (FCGR2A), Tn ag, Tim1-/HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Gonadotropin Hormone receptor (CGHR or GR), CCR4, GD3, SLAMF6, SLAMF4, HIV1 envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, KSHV K8.1, KSHV-gH, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), auto antibody to desmoglein 3 (Dsg3), auto antibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IgE, CD99, Ras G12V, Tissue Factor 1 (TF1), AFP, GPRCSD, Claudin18.2 (CLD18A2 or CLDN18A.2), P-glycoprotein, STEAP1, Livl, Nectin-4, Cripto, gpA33, BST1/CD157, low conductance chloride channel, and the antigen recognized by TNT antibody or combinations thereof. 
     981 In some embodiments, the antigens specific for a disease which may be targeted by the non-naturally occurring immune receptor, e.g, a CAR, when expressed alone or with the accessory modules as described herein include but are not limited to any one or more of 4-1BB, 5T4, adenocarcinoma antigen, alpha-fetoprotein, BAFF, B-lymphoma cell, C242 antigen, CA-125, carbonic anhydrase 9 (CA-IX), C-MET, CCR4, CD152, CD19, CD20, CD200, CD22, CD221, CD23 (IgE receptor), CD28, CD30 (TNFRSF8), CD33, CD4, CD40, CD44 v6, CD51, CD52, CD56, CD74, CD80, CD123, CEA, CNT0888, CTLA-4, DRS, EGFR, EpCAM, CD3, FAP, fibronectin extra domain-B, folate receptor 1, GD2, GD3 ganglioside, glycoprotein 75, GPNMB, HER2/neu, HGF, human scatter factor receptor kinase, IGF-1 receptor, IGF-I, IgG1, L1-CAM, IL-13, IL-6, insulin-like growth factor I receptor, integrin α5β1, integrin avβ3, LAMP1, MORAb-009, MS4A1, MUC1, mucin CanAg, N-glycolylneuraminic acid, NPC-1C, PDGF-R α, PDL192, phosphatidylserine, prostatic carcinoma cells, RANKL, RON, ROR1, SCH 900105, SDC1, SLAMF7, TAG-72, tenascin C, TGF beta 2, TGF-β, TRAIL-R1, TRAIL-R2, tumor antigen CTAA16.88, VEGF-A, VEGFR-1, VEGFR2, vimentin or combinations thereof. Other antigens specific for cancer will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the disclosure. 
     A CAR when used alone or with accessory modules as described herein can comprise an antigen binding domain (e.g., antibody or antibody fragment) that binds to a disease-supporting antigen (e.g., a disease-supporting antigen as described herein). In some embodiments, the disease-supporting antigen is an antigen present on cells that support the survival and proliferation of disease causing cells. In some embodiments, the disease-supporting antigen is an antigen present on a stromal cell or a myeloid-derived suppressor cell (MDSC). Stromal cells can secrete growth factors and cytokines to promote cell proliferation in the microenvironment. MDSC cells can block T cell proliferation and activation. Without wishing to be bound by theory, in some embodiments, the CAR-expressing cells destroy the disease-supporting cells, thereby indirectly blocking growth or survival of disease causing cells. 
     In certain embodiments, a stromal cell antigen is selected from one or more of: bone marrow stromal cell antigen 2 (BST2), fibroblast activation protein (FAP) and tenascin. In an embodiment, the FAP-specific antibody is, competes for binding with, or has the same CDRs as, sibrotuzumab. In embodiments, the MDSC antigen is selected from one or more of: CD33, CD11b, C14, CD15, and CD66b. Accordingly, in some embodiments, the disease supporting antigen is selected from one or more of: bone marrow stromal cell antigen 2 (BST2), fibroblast activation protein (FAP) or tenascin, CD33, CD11b, C14, CD15, and CD66b. 
     In another embodiment, the disclosure provides non-naturally occurring immune receptor, e.g, a CAR, that bind to the same epitope on different targets described in Tables 6A-C as any of the non-naturally occurring immune receptors of the disclosure (e.g., CARs that have the ability to cross-compete for binding to the different targets with any of the CARs of the disclosure). In some embodiments, the antigen specific domains of these non-naturally occurring immune receptors, e.g, a CARs, could be derived from vL fragments, vH fragments or scFv fragments of antibodies. In some embodiments, the reference antibodies for cross-competition studies to determine the target-epitope recognized by a non-naturally occurring immune receptor, e.g, a CAR, of the disclosure are scFvs described in Table 6C herein having sequences as shown in SEQ ID NOs: 4555-4815, 11165-11401, 15070-15132 (Table 6C) or as described in Tables 5-6 of PCT/US2017/064379. In an exemplary embodiment, the reference scFv FMC63(vL-vH) represented by SEQ ID NO: 4555 can be used in cross-competiton studies to to determine the target-epitope recognized by FMC63-based conventional CARs and backbones of the disclosure. In some embodiments, the reference vHH fragments for cross-competition studies to determine the target-epitope recognized by a non-naturally occurring immune receptor, e.g, a CAR, of the disclosure described herein are vHH fragments having sequences as shown in SEQ ID NOs: 4474-4514 . In some embodiments, the reference non-immunoglobulin antigen binding scaffolds for cross-competition studies for cross-competition studies to determine the target-epitope recognized by a non-naturally occurring immune receptor, e.g, a CAR, of the disclosure described heriin are non-immunoglobulin antigen binding scaffolds having sequences as shown in SEQ ID NOs: 4515-4519. In some embodiments, the reference ligands for cross-competition studies to determine the target-epitope recognized by a CAR of the disclosure described herein are ligands having sequences whose SEQ ID Nos: 4544-4554. In some embodiments, the reference CARs for cross-competition studies against different targets are CARs whose SEQ IDs are shown in Tables 10-14. 
     In another embodiment, the reference antibodies for cross-competition studies to determine the target-epitopes recognized by the MPL-targeting CARs of the disclosure are antibodies mAb-1.6, mAb-1.111, mAb-1.75, mAb-1.78, mAb-1.169, and mAb-1.36 described in patent application US 2012/0269814 A1. 
     In another embodiment, the reference scFvs for cross-competition studies to determine the target-epitopes recognized by the MPL-targeting CARs of the disclosure are scFvs having sequences as shown in SEQ ID NOs: 4720-4727, in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. 
     In another embodiment, the reference ligands for cross-competition studies to determine the target-epitopes recognized by the MPL-targeting CARs of the disclosure are TPO and mTPO ligands having sequences as listed in SEQ ID NOs: 4544-4545. 
     In another embodiment, the reference CARs for cross-competition studies to determine the target-epitopes recognized by the MPL-targeting CARs of the disclosure are CARs having sequences as shown in SEQ ID NOs: 5120-5126. 
     In the preferred embodiment, the MPL-targeting CARs of the disclosure bind to an epitope corresponding to the sequences shown in SEQ ID NO: 15160. 
     In one embodiment, the reference scFvs for cross-competition studies to determine the target-epitopes recognized by the CD19-targeting CARs of the invention are scFvs having sequences as shown in SEQ ID NOs: 4555-4568 and in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies to determine the target-epitopes recognized by the CD19-targeting CARs of the invention are CARs having sequences as shown in SEQ ID NOs: 4929-4943. 
     In one embodiment, the reference scFvs for cross-competition studies to determine the target-epitopes recognized by the CD20-targeting CARs of the invention are scFvs targeting CD20 and having SEQ IDs as listed in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies to determine the target-epitopes recognized by the CD20-targeting CARs of the invention are CARs targeting CD20 and having SEQ IDs as listed in Tables 12. 
     In the preferred embodiment, the CD20-targeting CARs of the disclosure bind to the epitopes corresponding to one or more of the sequences shown in SEQ ID NO: 15149-15154. 
     In one embodiment, the reference scFvs for cross-competition studies to determine the target-epitopes recognized by the BCMA-targeting CARs of the invention are scFvs targeting CD20 and having SEQ IDs as listed in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies to determine the target-epitopes recognized by the BCMA-targeting CARs of the invention are CARs targeting BCMA and having SEQ IDs as listed in Tables 12. 
     In the preferred embodiment, the BCMA-targeting CARs of the disclosure bind to the epitopes corresponding to one or more of the sequences shown in SEQ ID NO: 15155-15159. 
     In one embodiment, the reference scFvs for cross-competition studies against DLL3-targeting CARs of the invention are scFvs targeting DLL3 and having SEQ IDs as listed in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies against DLL3-targeting CARs of the invention are CARs targeting DLL3 and having SEQ IDs as listed in Table 12. 
     In one embodiment, the reference scFvs for cross-competition studies against LAMP1-targeting CARs of the invention are scFvs targeting LAMP1 and having SEQ IDs as listed in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies against LAMP1-targeting CARs of the invention are CARs targeting LAMP1 and having SEQ IDs as listed in Table 12. 
     In one embodiment, the reference scFvs for cross-competition studies against TROP2-targeting CARs of the invention are scFvs targeting TROP2 and having SEQ IDs as listed in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies against TROP2-targeting CARs of the invention are CARs targeting TROP2 and having SEQ IDs as listed in Table 12. 
     In one embodiment, the reference scFvs for cross-competition studies against PTK7-targeting CARs of the invention are scFvs targeting PTK7 and having SEQ IDs as listed in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies against PTK7-targeting CARs of the invention are CARs targeting PTK7 and having SEQ IDs as listed in Table 12. 
     In one embodiment, the reference scFvs for cross-competition studies against CD22, CD123, CD33, CD37, CD70, CD138, CS1, IL13Ra2, Folate Receptor a, Folate Receptor (3, TCRB1, TCRB2, TCRγδ, CD30, Mesothelin, Her2, EGFRviii, and HIV1-targeting CARs of the invention are scFvs targeting these antigens and having SEQ IDs as listed in Table 6C or as described in Tables 5-6 of PCT/US2017/064379. In another embodiment, the reference CARs for cross-competition studies against CD22, CD123, CD33, CD37, CD70, CD138, CS1, IL13Ra2, Folate Receptor a, Folate Receptor (3, TCRB1, TCRB2, TCRγδ, CD30, Mesothelin, Her2, EGFRviii, and HIV1-targeting CARs of the invention are CARs targeting these antigens and having SEQ IDs as listed in Table 12. 
     In some embodiments, the CARs described herein comprise a hinge or linker region between the antigen specific domain and the transmembrane domain. In some embodiments, the hinge region comprises any one or more of human CD8α or an Fc fragment of an antibody or a functional equivalent, fragment or derivative thereof, a hinge region of human CD8α or an antibody or a functional equivalent, fragment or derivative thereof, a CH2 region of an antibody, a CH3 region of an antibody, an artificial spacer sequence and combinations thereof. In exemplary embodiments, the hinge region comprises any one or more of (i) a hinge, CH2 and CH3 region of IgG4, (ii) a hinge region of IgG4, (iii) a hinge and CH2 region of IgG4, (iv) a hinge region of CD8a, (v) a hinge, CH2 and CH3 region of IgG1, (vi) a hinge region of IgG1, (vi) a hinge and CH2 region of IgG1, or (vii) combinations thereof. 
     In some embodiments, two or more functional domains of the non-naturally occurring immune receptors, e.g., CARs, as described herein, are separated by one or more linkers. Linkers are oligo- or polypeptides region from about 1 to 100 amino acids in length, that link together any of the domains/regions of the non-naturally occurring immune receptors, e.g., CARs, of the disclosure. In some embodiments, the linkers may be for example, 5-12 amino acids in length, 5-15 amino acids in length or 5-20 amino acids in length. Linkers may be composed of flexible residues like glycine and serine so that the adjacent protein domains are free to move relative to one another. Longer linkers, for example those longer than 100 amino acids, may be used in connection with alternate embodiments of the disclosure, and may be selected to, for example, ensure that two adjacent domains do not sterically interfere with one another. 
     As described herein, the CARs described herein comprise a transmembrane domain. The transmembrane domain may comprise the transmembrane sequence from any protein which has a transmembrane domain, including any of the type I, type II or type III transmembrane proteins. The transmembrane domain of the CAR of the disclosure may also comprise an artificial hydrophobic sequence. The transmembrane domains of the CARs described herein may be selected so that the transmembrane domain do not dimerize. In some embodiments, the CAR comprises any of the backbones described herein having a transmembrane domain selected from the transmembrane domain of an alpha, beta or zeta chain of a T-cell receptor, CD3ε, CD3ζ, CD3γ, CD3δ, CD28, CD45, CD4, CDS, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, KIRDS2, OX40, CD2, CD27, LFA-1 (CD1 la, CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD40, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), CD160, CD19, IL2R beta, IL2R gamma, IL7R a, ITGA1, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD1 ld, ITGAE, CD103, ITGAL, CD1 1a, LFA-1, ITGAM, CD1 1b, ITGAX, CD1 1c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, DNAM1(CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRT AM, Ly9 (CD229), CD160 (BY55), PSGL1, CDIOO (SEMA4D), SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, PAG/Cbp, NKp44, NKp30, NKp46, NKG2D, and/or NKG2C. 
     A transmembrane domain can include one or more additional amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 up to 15 amino acids) at either end of the transmembrane region (e.g., one or more amino acids extending extracellularly and/or one or more amino acids extending intracellularly) to the transmembrane region. In one aspect, the transmembrane domain is contiguous with one of the other domains of the CAR. In one embodiment, the transmembrane domain may be from the same protein that the signaling domain, costimulatory domain or the hinge domain is derived from. In another aspect, the transmembrane domain is not derived from the same protein that any other domain of the CAR is derived from. 
     In various embodiments, the isolated nucleic acid molecules encoding the non-naturally occurring immune receptors, e.g., CAR, components of the backbones described herein, encode zero, one, two, three or more intracellular signaling domain. 
     As described herein, the non-naturally occurring immune receptors, e.g., CARs, described herein can optionally comprise an intracellular signaling domain. This domain may be cytoplasmic and may transduce the effector function signal and direct the cell to perform its specialized function. Examples of intracellular signaling domains include, but are not limited to, ζ chain of the T-cell receptor or any of its homologs (e.g., r l  chain, CD3E, CD3γ, CD3δ, FccR1γ and β chains, MB1 (Igα) chain, B29 (Igβ) chain, etc.), CD3 polypeptides (Δ, δ and ε), syk family tyrosine kinases (Syk, ZAP 70, etc.), src family tyrosine kinases (Lck, Fyn, Lyn, etc.) and other molecules involved in T-cell transduction, such as CD2, CD5 and CD28. Specifically, the intracellular signaling domain may be human CD3 zeta chain, FcyRIII, FccRI, cytoplasmic tails of Fc receptors, immunoreceptor tyrosine-based activation motif (ITAM) bearing cytoplasmic receptors or combinations thereof. Additional intracellular signaling domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention. In some embodiments, the intracellular signaling domain comprises a signaling domain of one or more of a human CD3 zeta chain, FcgRIII, FceRT, a cytoplasmic tail of a Fc receptor, an immunoreceptor tyrosine-based activation motif (ITAM) bearing cytoplasmic receptors, and combinations thereof. 
     In various embodiments, the isolated nucleic acid molecules encoding the non-naturally occurring immune receptor, e.g., CAR, components of the backbones described herein, encode zero, one, two, three or more co-stimulatory domains. In exemplary embodiments, the co-stimulatory domain comprises a signaling domain from any one or more of CD28, CD137 (4-1BB), CD134 (0X40), Dap10, CD27, CD2, CD5, ICAM-1, LFA-1, Lck, TNFR-I, TNFR-II, Fas, CD30, CD40 and combinations thereof arious components of non-naturally occurring immune receptors, e.g., CARs, of the disclosure are provided above and elsewhere herein. Again it shoud be recognized that the disclosure provides, for example, CARs comprising an ecto-domain comprising an antigen specific binding domain attached via a ‘hinge’ of linker to a transmembrane domain, which is in-turn linked to an endo-domain comprising one or more stimulatory domains and optionally one or more intracellular signaling domains. 
     Provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding conventional CARs 1 to 6 (Table 1) or any one or more of backbones 1-72 described herein (Table 2). 
     Also provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding conventional CARs 1 to 6. In some embodiments, the antigen-specific domain of the CARs is specific to one, two, three or more antigens on target cells, such as cancer cells. As described herein, each component of the CAR is contiguous and in the same reading frame with each other components of the CAR. In some embodiments, in the CAR comprising backbone comprises more than one antigen specific domain, each of the antigen specific domains are contiguous and in the same reading frame as the other antigen specific domains in the same CAR. 
     Also provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding backbones 1 to 10 comprising conventional CAR I and an accessory module encoding a NF-κB stimulatory molecule (e.g., vFLIP-K13, hNEMO-K277A, FKBPx2-hNEMO-K277A, FKBPx2-hNEMO-L753(251), FKBPx2-hNEMO-L600(200), FKBPx2-RIP-ID, IKK2-S177E-S181E, IKK1-S176E-S180E, MyD88-L265P, TCL-1A or their variants) as described herein. The accessory module in backbones 1-10 can be replaced by other accessory modules encoding different molecules, including different NF-κB activators (e.g., K13-opt, hNEMO-K277A-delta-V249-K255 or hNEMO-K277L etc.). Also provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding backbones 11 to 12 comprising conventional CAR I and an accessory module encoding IgSP-[hTRAC-opt2] and IgSP-[hTRBC-opt2]. In some embodiments, the antigen-specific domain of the CAR comprising backbones-1-12 is specific to one, two, three or more antigens on target cells, such as cancer cells. As described herein, each component of the CAR is contiguous and in the same reading frame with each other components of the CAR comprising backbones 1-12. In some embodiments, in the CAR comprising backbones 1-12 comprises more than one antigen specific domain, each of the antigen specific domains are contiguous and in the same reading frame as the other antigen specific domains in the same CAR. 
     Also provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding backbones 13 to 22 comprising conventional CAR II and an accessory module encoding a NF-κB stimulatory molecule (e.g., vFLIP-K13, hNEMO-K277A, FKBPx2-hNEMO-K277A, FKBPx2-hNEMO-L753(251), FKBPx2-hNEMO-L600(200), FKBPx2-RIP-ID, IKK2-S177E-S181E, IKK1-S176E-S180E, MyD88-L265P, TCL-1A or their variants) as described herein. The accessory module in backbones 13-22 can be replaced by other accessory modules encoding different molecules, including different NF-κB activators (e.g., K13-opt, hNEMO-K277A-delta-V249-K255 or hNEMO-K277L etc.). In some embodiments, the antigen-specific domain of the CAR comprising backbones-13-22 is specific to one, two, three or more antigens on target cells, such as cancer cells. As described herein, each component of the CAR is contiguous and in the same reading frame with each other components of the CAR comprising backbones 13-24. In some embodiments, in the CAR comprising backbones 13-24 comprises more than one antigen specific domain, each of the antigen specific domains are contiguous and in the same reading frame as the other antigen specific domains in the same CAR. 
     Also provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding backbones 37 to 46 comprising Ab-TCR and an accessory module encoding a NF-κB stimulatory molecule (e.g., vFLIP-K13, hNEMO-K277A, FKBPx2-hNEMO-K277A, FKBPx2-hNEMO-L753(251), FKBPx2-hNEMO-L600(200), FKBPx2-RIP-ID, IKK2-S177E-S181E, IKK1-S176E-S180E, MyD88-L265P, TCL-1A or their variants) as described herein. The accessory module in backbones 37 to 46 can be replaced by other accessory modules encoding different molecules, including different NF-κB activators (e.g., K13-opt, hNEMO-K277A-delta-V249-K255 or hNEMO-K277L etc.). 
     Also provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding backbones 49 to 58 comprising double chain cTCR/SIR and an accessory module encoding a NF-κB stimulatory molecule (e.g., vFLIP-K13, hNEMO-K277A, FKBPx2-hNEMO-K277A, FKBPx2-hNEMO-L753(251), FKBPx2-hNEMO-L600(200), FKBPx2-RIP-ID, IKK2-S177E-S181E, IKK1-S176E-S180E, MyD88-L265P, TCL-1A or their variants) as described herein. The accessory module in backbones 49 to 58 can be replaced by other accessory modules encoding different molecules, including different NF-κB activators (e.g., K13-opt, hNEMO-K277A-delta-V249-K255 or hNEMO-K277L etc.). 
     Also provided herein are one or more polypeptides encoded by one or more nucleic acid molecules encoding backbones 61 to 70 comprising one-and-a-half chain (OHC) cTCR/SIR and an accessory module encoding a NF-κB stimulatory molecule (e.g., vFLIP-K13, hNEMO-K277A, FKBPx2-hNEMO-K277A, FKBPx2-hNEMO-L753(251), FKBPx2-hNEMO-L600(200), FKBPx2-RIP-ID, IKK2-S177E-S181E, IKK1-S176E-S180E, MyD88-L265P, TCL-1A or their variants) as described herein. The accessory module in backbones 61 to 70 can be replaced by other accessory modules encoding different molecules, including different selective NF-κB activators (e.g., K13-opt, hNEMO-K277A-delta-V249-K255 or hNEMO-K277L etc.). 
     In various embodiments, the polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, comprise one, two, three or more NF-κB stimulatory molecule (e.g., K13-vFLIP, K13opt, NEMO, NEMO K277A, human NEMO-K277L, human NEMO-K277A-DeltaV249-K255, or mouse NEMO K270A or their variants). 
     In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of the backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to the thrombopoietin receptor, MPL. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD19. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD20. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD22. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD23 In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD30. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD32. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD33. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD123. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD138. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD200R. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD276. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD324. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to BCMA. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CS1. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to ALK1. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to ROR1. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CDH6 In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CDH16. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CDH17. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CDH19. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to EGFRviii. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Her2. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Her3. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Mesothelin. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Folate Receptor alpha. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Folate Receptor beta. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CLL-1. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CLEC5A. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to NY-ESO/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to WT1/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to WT1/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to AFP/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to HPV16-E7/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to gp100/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to hTERT/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to MART1/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to HTLV1-Tax/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to PR1/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to HIV1-gag/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to HIV1-envelop gp120. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to DLL3. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to PTK7. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to TROP2. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to LAMP1. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Timl. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to TCR gamma-delta. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to TCR betal constant chain. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to TCR beta2 constant chain. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to GCC. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to B7H4. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to LHR. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to TSHR. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Tn-Mucl. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to TSLPR. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Tissue Factor. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to SSEA-4. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-32 or backbone-33, wherein the antigen-specific domain of the CARs is specific to SLea. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Mucl/MHC class I complex. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Muc16. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to NYBR-1. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to IL13Ra2. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to IL11Ra. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to L1CAM. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to EpCAM1. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to gpNMB. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to GRP78. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to GPC3. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to GRPC5D. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to GFRa4. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to FITC. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD79b. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Lyml. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Lym2. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 4 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CLD18A2. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 4 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD43 epitope expressed on leukemia cells. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 4 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to CD179a. In some embodiments, provided herein are polypeptides encoded by the nucleic acid molecules encoding CARs which are part of the conventional CARs 1 to 6 or are part of backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, wherein the antigen-specific domain of the CARs is specific to Fc portion of an antibody (i.e. Ig Fc). An exemplary CAR with the antigen-specific domain specific to Ig Fc is represented by SEQ ID NO: 1629 and contains the extracellular domain of CD16-V158 as the antigen specific domain. In any of the foregoing, the nucleic acid molecule encoding the CAR construct further comprise a NF-κB activator coding sequence, or alternatively, a NF-κB activator coding sequence can be present on a second nucleic acid molecule. 
     The nucleic acid sequences encoding for the desired components of the non-naturally occurring immune receptors, e.g., CARs, and/or a selective NF-κB activator coding sequence described herein can be obtained using recombinant methods known in the art, such as, for example by screening libraries from cells expressing the nucleic acid molecule, by deriving the nucleic acid molecule from a vector known to include the same, or by isolating directly from cells and tissues containing the same, using standard techniques. Alternatively, the nucleic acid of interest can be produced synthetically, rather than cloned. 
     In some embodiments, the nucleic acid molecule encoding the non-naturally occurring immune receptors, e.g., CARs, and/or accessory molecules (e.g., a NF-κB activator sequence) described herein is provided as a messenger RNA (mRNA) transcript. In another embodiment, the nucleic acid molecule encoding the non-naturally occurring immune receptors, e.g., CARs, and/or accessory molecules (e.g., a selective NF-κB activator coding sequence) described herein is provided as a DNA construct. 
     Cloning and expression methods will be apparent to a person of skill in the art and may be as described in WO 2015/142675; Sambrook et al., 2012, MOLECULAR CLONING: A LABORATORY MANUAL, volumes 1-4, Cold Spring Harbor Press, N.Y.; June et al. 2009 Nature Reviews Immunology 9.10: 704-716; WO 01/96584; WO 01/29058; U.S. Pat. No. 6,326,193, the contents of each of which are herein incorporated by reference in their entirety as though set forth herein. Physical methods for introducing polynucleotides of into host cells such as calcium phosphate transfection and the like are well known in the art and will be apparent to a person of skill in the art. In exemplary embodiments, such methods are set forth in Sambrook et al., 2012, MOLECULAR CLONING: A LABORATORY MANUAL, volumes 1-4, Cold Spring Harbor Press, NY); U.S. Pat. Nos. 5,350,674 and 5,585,362, the contents of each of which are herein incorporated by reference in their entirety as though set forth herein. In another embodiment, a CAR vector is transduced into a cell, e.g., a T cell or a NK cell, by causing transient perturbations in cell membrane using a microfluid device as described in patent application WO 2013/059343 Al (PCT/US2012/060646) and in Ding X et al, Nat. Biomed. Eng. 1, 0039 (2017) the contents of each of which are herein incorporated by reference in their entirety as though set forth herein. 
     The disclosure provides a recombinant nucleic acid construct comprising a nucleic acid molecule encoding a non-naturally occurring immune receptor, e.g., CAR, wherein the nucleic acid molecule comprises a nucleic acid sequence encoding one or more antigen binding domains, wherein the nucleotide sequences encoding each of the antigen binding domains are contiguous with and in the same reading frame as the nucleic acid sequences encoding a: (i) optional hinge/linker, (ii) transmembrane domain, and (iii) optional intracellular domain, or (a) a T cell receptor constant chain. An exemplary T cell receptor constant chain that can be used in the construction of SIR includes, but is not limited to, constant chain of TCRα. TCRβ1, TCRβ2, TCRγ, TCRγ, preTCRα and variants and mutants thereof. In some embodiments, a NF-κB activator (e.g., a selective NF-κB activator) coding sequence is on the same recombinant nucleic acid construct but upon expression is not linked to the non-naturally occurring immune receptor, e.g., CAR, but is rather cleaved off (e.g., via a peptide cleavable linker) or is part of its own expression cassette in the polynucleotide. 
     The disclosure also provides a vector or vectors comprising a nucleic acid sequence or sequences encoding a non-naturally occurring immune receptor, e.g., CAR, described herein and an accessory module. In some embodiments, the accessory module encodes a NF-κB activator, e.g., a selective NF-κB activator. In some embodiment, the selective NF-κB activator is a non-naturally occurring NF-κB activator. In one embodiment, the non-naturally occurring immune receptor, e.g., CAR, and the accessory module, e.g., an accessory module encoding a NF-κB activator, are encoded by a single vector. In another embodiment, the non-naturally occurring immune receptor, e.g., CAR, and the accessory module, e.g., an accessory module encoding a NF-κB activator, are encoded by more than one vector. In yet another embodiment, a non-naturally occurring immune receptor, e.g., CAR, and the accessory module, e.g., an accessory module encoding a NF-κB activator, are each encoded by a separate vector or by separate nucleic acids. In one embodiment, the two functional polypeptide units (e.g, CAR and accessory module) are encoded by a single vector or a single nucleic acid. In one embodiment, the vector or the vectors are chosen from DNA vector(s), RNA vector(s), plasmid(s), lentivirus vector(s), adenoviral vector(s), retrovirus vector(s), baculovirus vector(s), sleeping beauty transposon vector(s), or a piggyback transposon(s). In one embodiment, the vector is a lentivirus vector or a retroviral vector. In another embodiment, the vector is a sleeping beauty transposon vector. The nucleic acid sequences of exemplary vectors are provided in SEQ ID NO: 3840-3841. The vectors pLenti-EF1α (SEQ ID NO: 3840) and pLenti-EF1a-DWPRE (SEQ ID NO: 3841) are empty lentiviral vectors that differ by the fact that pLenti-EF1a-DWPRE lacks the WPRE region. The nucleic acid sequence of pCCL3-MNDU3-WPRE vector is given in SEQ ID NO: 7779. A non-naturally occurring immune receptor coding sequence of the disclosure can be cloned between the Nhe I and Sal I sites in these vectors. 
     A retroviral vector may also be, e.g., a gammaretroviral vector. A gammaretroviral vector may include, e.g., a promoter, a packaging signal (ψ), a primer binding site (PBS), one or more (e.g., two) long terminal repeats (LTR), and a transgene of interest, e.g., a gene encoding a non-naturally occurring immune receptor, e.g., CAR. A gammaretroviral vector may lack viral structural gens such as gag, pol, and env. Exemplary gammaretroviral vectors include Murine Leukemia Virus (MLV), Spleen-Focus Forming Virus (SFFV), and Myeloproliferative Sarcoma Virus (MPSV), and vectors derived therefrom. Other gammaretroviral vectors are described, e.g., in Tobias Maetzig et al., “Gammaretroviral Vectors: Biology, Technology and Application” Viruses. 2011 Jun., 3 (6): 677-713. In another embodiment, the vector comprising the nucleic acid encoding the desired non-naturally occurring immune receptors of the disclosure is an adenoviral vector (A5/35). 
     In some embodiments, a vector of the disclosure can further comprise a promoter. Non-limiting examples of a promoter include, for example, a MNDU3 promoter, a CMV IE gene promoter, an EF-la promoter, an ubiquitin C promoter, a core-promoter or a phosphoglycerate kinase (PGK) promoter. In some embodiments, the promoter is an EF-1 promoter. In some embodiments, the vector comprises a poly(A) tail. In some embodiments, the vector comprises a 3′UTR. 
     The disclosure also includes an RNA construct that can be directly transfected into a cell. A method for generating mRNA for use in transfection involves in vitro transcription (IVT) of a template with specially designed primers, followed by poly A addition, to produce a construct containing 3′ and 5′ untranslated sequence (“UTR”) (e.g., a 3′ and/or 5′ UTR described herein), a 5′ cap (e.g., a 5′ cap described herein) and/or Internal Ribosome Entry Site (IRES) (e.g., an IRES described herein), the nucleic acid to be expressed, and a poly A tail, typically 50-2000 bases in length (SEQ ID NO:3855). RNA so produced can efficiently transfect different kinds of cells. In one embodiment, the template includes sequences for the non-naturally occurring immune receptor, e.g., CAR, and/or the NF-κB stimulatory molecule. In one embodiment, an RNA CAR-NFKB vector is transduced into a cell, e.g., a T cell or a NK cell, by electroporation. In another embodiment, an RNA CAR vector and/or a NF-κB activator vector is transduced into a cell, e.g., a T cell or a NK cell, by causing transient perturbations in cell membrane using a microfluid device. The different chains (or functional polypeptide units) can be also introduced in a cell using one or more than one vector a combination of different vectors or techniques. In another embodiment, a non-naturally occurring immune receptor, e.g., CAR, can be introduced using a retroviral vector while the accessory module encoding a NF-κB activator is introduced using a lentiviral vector. In another aspect, a non-naturally occurring immune receptor, e.g., CAR, is introduced using a lentiviral vector while the accessory module (e.g., a NF-κB activator) is introduced using a sleeping beauty transposon. In yet another aspect, a non-naturally occurring immune receptor, e.g., CAR, is introduced using a lentiviral vector while the accessory module (e.g., a NF-κB activator) is introduced using a RNA transfection. In yet another aspect, a non-naturally occurring immune receptor, e.g., CAR, is produced in a cell by genetic recombination at the endogeneous TCR chain loci using gene targeting techniques known in the art while the accessory module is introduced using a lentiviral or a retroviral vector. RNA can be introduced into target cells using any of a number of different methods, for instance, commercially available methods which include, but are not limited to, electroporation (Amaxa Nucleofector-II (Amaxa Biosystems, Cologne, Germany)), (ECM 830 (BTX) (Harvard Instruments, Boston, Mass.) or the Gene Pulser II (BioRad, Denver, Colo.), Multiporator (Eppendort, Hamburg Germany), cationic liposome mediated transfection using lipofection, polymer encapsulation, peptide mediated transfection, or biolistic particle delivery systems such as “gene guns” (see, for example, Nishikawa, et al. Hum Gene Ther., 12(8):861-70 (2001) or by causing transient perturbations in cell membranes using a microfluidic device (see, for example, patent applications WO 2013/059343 A1 and PCT/US2012/060646). 
     In some embodiments, the non-viral method includes the use of a transposon (also called a transposable element). In some embodiments, a transposon is a piece of DNA that can insert itself at a location in a genome, for example, a piece of DNA that is capable of self-replicating and inserting its copy into a genome, or a piece of DNA that can be spliced out of a longer nucleic acid and inserted into another place in a genome. For example, a transposon comprises a DNA sequence made up of inverted repeats flanking genes for transposition. 
     Exemplary methods of nucleic acid delivery using a transposon include a Sleeping Beauty transposon system (SBTS) and a piggyBac (PB) transposon system. See, e.g., Aronovich et al. Hum. Mol. Genet. 20.R1(2011):R14-20; Singh et al. Cancer Res. 15(2008):2961-2971; Huang et al. Mol. Ther. 16(2008):580-589; Grabundzija et al. Mol. Ther. 18(2010):1200-1209; Kebriaei et al. Blood. 122.21(2013):166; Williams. Molecular Therapy 16.9(2008): 1515-16; Bell et al. Nat. Protoc. 2.12(2007):3153-65; and Ding et al. Cell. 122.3(2005):473-83, all of which are incorporated herein by reference. 
     The SBTS includes two components: 1) a transposon containing a transgene and 2) a source of transposase enzyme. The transposase can transpose the transposon from a carrier plasmid (or other donor DNA) to a target DNA, such as a host cell chromosome/genome. For example, the transposase binds to the carrier plasmid/donor DNA, cuts the transposon (including transgene(s)) out of the plasmid, and inserts it into the genome of the host cell. See, e.g., Aronovich et al. supra. 
     Exemplary transposons include a pT2-based transposon. See, e.g., Grabundzija et al. Nucleic Acids Res. 41.3(2013): 1829-47; and Singh et al. Cancer Res. 68.8(2008): 2961-2971, all of which are incorporated herein by reference. Exemplary transposases include a Tc 1/mariner-type transposase, e.g., the SB 10 transposase or the SB 11 transposase (a hyperactive transposase which can be expressed, e.g., from a cytomegalovirus promoter). See, e.g., Aronovich et al.; Kebriaei et al.; and Grabundzija et al., all of which are incorporated herein by reference. 
     Use of the SBTS permits efficient integration and expression of a transgene, e.g., a nucleic acid encoding a CAR and/or a NF-κB activator described herein. Provided herein are methods of generating a cell, e.g., T cell or NKT cell or stem cell or iPSC or synthetic T cell, that stably expresses a CAR and/or a NF-κB activator described herein, e.g., using a transposon system such as SBTS. 
     In accordance with methods described herein, in some embodiments, one or more nucleic acids, e.g., plasmids, containing the SBTS components are delivered to a cell (e.g., T or NKT cell or stem cell or iPSC or synthetic T cell). For example, the nucleic acid(s) are delivered by standard methods of nucleic acid (e.g., plasmid DNA) delivery, e.g., methods described herein, e.g., electroporation, transfection, or lipofection. In some embodiments, the nucleic acid contains a transposon comprising a transgene, e.g., a nucleic acid encoding a non-naturally occurring immune receptor, e.g., CAR, and/or a NF-κB activator described herein. In some embodiments, the nucleic acid contains a transposon comprising a transgene (e.g., a nucleic acid encoding a non-naturally occurring immune receptor, e.g., CAR, and/or a NF-κB activator described herein) as well as a nucleic acid sequence encoding a transposase enzyme. In other embodiments, a system with two nucleic acids is provided, e.g., a dual-plasmid system, e.g., where a first plasmid contains a transposon comprising a transgene, and a second plasmid contains a nucleic acid sequence encoding a transposase enzyme. For example, the first and the second nucleic acids are codelivered into a host cell. 
     As described above and elsewhere herein, the disclosure demonstrates that co-expression of an immune receptor (e.g, a CAR, an endogenous TCR or a recombinant TCR) of the disclosure with an NF-κB stimulatory molecule (e.g., a selective NF-κB activator, e.g., a non-naturally occurring NF-κB activating agent, e.g., hNEMO-K277A) improves the functions of immune cells such as survival, expansion, proliferation, activation, persistence, cytokine production and in vivo activity. In some embodiments, the immune receptor is a non-naturally occurring immune receptor (e.g., CAR or recombinant TCR). In some embodiments, the immune receptor is a naturally occurring immune receptor (e.g., a native TCR). In one embodiment, an NF-κB stimulatory molecule is co-expressed with a first generation, second generation, third generation CAR, TFP, AbTCR, or SIR. As mentioned above, the NF-κB stimulatory molecule can be, but preferably is not, linked to a CAR, TCR or SIR backbone. Moreover, in certain embodiments, a CAR of the disclosure does not include a CD28 or 41BB domain, and optionally includes a CD3 domain. 
     In one embodiment, the disclosure demonstrates that expression of a selective NF-κB activator improves the functions of immune cells (e.g., T cells, dendritic cells, CAR-T cells or TCR-T cells etc.) such as survival, expansion, proliferation, activation, persistence, cytokine production and in vivo activity. A selective NF-κB activator as described herein, refers to an agent that activates the NF-κB signaling pathway selectively with no or minimal activation of the other signaling pathways. In one embodiment, a selective NF-κB activator activates NF-κB signaling pathway with no or minimal activation of one or more of signaling pathways selected from the group of AKT, PI3K, JNK, p38 kinase, ERK, JAK/STAT and interferon signaling pathways. A number of methods to measure the activation of the NF-κB, AKT, PI3K, JNK, p38 kinase, ERK, JAK/STAT and interferon signaling pathways are known in the art. These assays can be used in the methods of the disclosure either singly or in combinations to identify selective activators of NF-κB pathway. 
     In one embodiment, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the AKT pathway as measured using Phospho-Akt (Ser473) antibody (Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the JNK pathway as measured using Phospho-SAPK/JNK (Thr183/Tyr185) antibody (e.g., clone G9; Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the p38 kinase pathway as measured using Phospho-p38 MAPK (Thr180/Tyr182) antibody (e.g., clone D3F9; Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Statl (Tyr701) antibody (e.g., Clone D4A7; Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Stat2 (Tyr690) antibody (Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Stat3 (Tyr705) antibody (e.g., Clone D3A7, Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Stat5 (Tyr694) antibody (e.g., Clone D47E7, Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-NF-κB p65 (Ser536) antibody (Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the ERK pathway as measured using Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (e.g., Clone D13.14.4E, Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. 
     In one embodiment, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-IκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) subunit but less than 20% increase in the activity of the AKT pathway as measured using Phospho-Akt (Ser473) antibody (Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. 
     In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-IκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the JNK pathway as measured using Phospho-SAPK/JNK (Thr183/Tyr185) antibody (e.g., clone G9; Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-IκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the p38 kinase pathway as measured using Phospho-p38 MAPK (Thr180/Tyr182) antibody (e.g., clone D3F9; Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-IκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Statl (Tyr701) antibody (e.g., Clone D4A7; Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-IκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Stat2 (Tyr690) antibody (Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-IκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Stat3 (Tyr705) antibody (e.g., Clone D3A7, Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by PhosphoIκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the STAT pathway as measured using Phospho-Stat5 (Tyr694) antibody (e.g., Clone D47E7, Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. In some embodiments, a selective NF-κB activator induces more than 20% (e.g., more than 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%) increase in NF-κB activity as measured by Phospho-IκBα (Ser32) antibody (e.g., 14D4, Clone Cell Signaling Technology; Danvers, Mass.) but less than 20% increase in the activity of the ERK pathway as measured using Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (e.g., Clone D13.14.4E, Cell Signaling Technology; Danvers, Mass.) when exposed to or expressed in a test human T cell as compared to a control human T cell. 
     Alternate methods of measuring the activation of the NF-κB, AKT, JNK, p38, ERK, JAK/STAT and interferon signaling pathways are known in the art and can be used to identify selective activator of the NF-κB signaling pathway. For example, a selective NF-κB activator induces greater increase in the NF-κB DNA binding activity when exposed to or expressed in a target cell (e.g., a T cell or 293FT cell) as compared to increase in c-Jun, c-Fos, JunD, ATF2, STAT3, NFAT1c, ELK-1, CREB, IRF3 or IRF7 DNA binding activities. Kits to measure DNA binding activities of different transcription factors belonging to different signaling pathways are available commercially (e.g., TransAM® Transcription Factor Assays; Active Motif) and can be used to identify selective activator of the NF-κB signaling pathway. 
     In an embodiment, a selective NF-κB activator induces greater increase in the ratio of increase in IκBα phosphorylation to increase in AKT phosphorylation as compared to CD28 when both of them are expressed in human T cells or when signaling through both is activated in human T cells under comparable conditions. In an embodiment, a selective NF-κB activator induces greater fold increase in the ratio of increase in IκBα phosphorylation to increase in AKT phosphorylation as compared to 41BB when both of them are expressed in human T cells under comparable conditions or when signaling through both is activated in human T cells under comparable conditions. In an embodiment, a selective NF-κB activator when co-expressed with a 1″ generation CAR lacking a costimulatory domain induces greater increase in the ratio of increase in IκBα phosphorylation to increase in AKT phosphorylation as compared to a 2nd generation CAR containing a CD28 costimulatory domain when both of them are expressed in human T cells and exposed to target antigen containing cells under comparable conditions. In an embodiment, a selective NF-κB activator when co-expressed with a 1″ generation CAR lacking a costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1016) induces greater increase in the ratio of increase in IκBα phosphorylation to increase in AKT phosphorylation as compared to a 2nd generation CAR containing a 41BB costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1318) when both of them are expressed in human T cells and exposed to target antigen containing cells (e.g., RAJI) under comparable conditions. For example, T cells expressing the CD19-directed first generation CAR co-expressing K13 (CD8SP-FMC63-(vL-vH)-Myc-z-P2A-K13-Flag-T2A-PAC; SEQ ID NO: 1016) show greater increase in the ratio of IκBα phosphorylation to AKT phosphorylation as compared to T cells expressing the CD19-directed 2nd generation CAR with 41BB costimulatory domain (CD8SP-FMC63-(vL-vH)-Myc-BBz-T2A-PAC; SEQ ID NO: 1318) when both the CAR-T cells are exposed to RAJI cells at E:T ratio of 1:5 for between 1-24 hours. The phosphorylation of IκBα and AKT are calculated by using methods known in the art (e.g., immunoblotting or Flow cytometry) using antibodies specific to their phosphorylated forms. The increase in IκBα phosphorylation is calculated by subtracting the IκBα phosphorylation in control T cells lacking the expression of CAR from the IκBα phosphorylation in CAR-T cells after exposure to RAJI cells. The increase in AKT phosphorylation is calculated by subtracting the AKT phosphorylation in control T cells lacking the expression of CAR from the AKT phosphorylation in CAR-T cells after exposure to RAJI cells. The ratio of increase in IκBα to increase in AKT phosphorylation is calculated by dividing the increase in IκBα phosphorylation from the increase in AKT phosphorylation. 
     In an embodiment, a selective NF-κB activator induces greater increase in the ratio of increase in p65/RelA phosphorylation to increase in AKT phosphorylation as compared to CD28 when both of them are expressed in human T cells or when signaling through both is activated in human T cells under comparable conditions. In an embodiment, a selective NF-κB activator induces greater fold increase in the ratio of increase in p65/RelA phosphorylation to increase in AKT phosphorylation as compared to 41BB when both of them are expressed in human T cells under comparable conditions or when signaling through both is activated in human T cells under comparable conditions. In an embodiment, a selective NF-κB activator when co-expressed with a 1″ generation CAR lacking a costimulatory domain induces greater increase in the ratio of increase in p65/RelA phosphorylation to increase in AKT phosphorylation as compared to a 2nd generation CAR containing a CD28 costimulatory domain when both of them are expressed in human T cells and exposed to target antigen containing cells under comparable conditions. In an embodiment, a selective NF-κB activator when co-expressed with a 1″ generation CAR lacking a costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1016) induces greater increase in the ratio of increase in p65/RelA phosphorylation to increase in AKT phosphorylation as compared to a 2 nd  generation CAR containing a 41BB costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1318) when both of them are expressed in human T cells and exposed to target antigen containing cells (e.g., RAJI) under comparable conditions. For example, T cells expressing the CD19-directed first generation CAR co-expressing K13 (CD8SP-FMC63-(vL-vH)-Myc-z-P2A-K13-Flag-T2A-PAC; SEQ ID NO: 1016) show greater increase in the ratio of p65/RelA phosphorylation to AKT phosphorylation as compared to T cells expressing the CD19-directed 2nd generation CAR with 41BB costimulatory domain (CD8SP-FMC63-(vL-vH)-Myc-BBz-T2A-PAC; SEQ ID NO: 1318) when both the CAR-T cells are exposed to RAJI cells at an Effector:Target (E:T) ratio of 1:5 for between 1-24 hours (e.g., 1 hour, 2 hours, 4 hours, 12 hours, or 24 hours). The phosphorylation of p65/RelA and AKT are calculated by using methods known in the art (e.g., immunoblotting or Flow cytometry) using antibodies specific to their phosphorylated forms. The increase in p65/RelA phosphorylation is calculated by subtracting the p65/RelA phosphorylation in control T cells lacking the expression of CAR from the p65/RelA phosphorylation in CAR-T cells after both are exposed to RAJI cells. The increase in AKT phosphorylation is calculated by subtracting the AKT phosphorylation in control T cells lacking the expression of CAR from the AKT phosphorylation in CAR-T cells after both are exposed to RAJI cells. The ratio of increase in p65/RelA to increase in AKT phosphorylation is calculated by dividing the increase in p65/RelA phosphorylation from the increase in AKT phosphorylation. 
     In an embodiment, a selective NF-κB activator when co-expressed with a 1st generation CAR lacking a costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1016) induces greater increase in the ratio of increase in IκBα phosphorylation to increase in JNK, ERK, or p38 kinase phosphorylation as compared to a 2nd generation CAR containing a 41BB costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1318) when both of them are expressed in human T cells and exposed to target antigen containing cells (e.g., RAJI) for appropriate time interval (e.g., 1-24 hours) under comparable conditions. In an embodiment, a selective NF-κB activator when co-expressed with a 1st generation CAR lacking a costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1016) induces greater increase in the ratio of increase in p65/RelA phosphorylation to increase in JNK, ERK, or p38 kinase phosphorylation as compared to a 2nd generation CAR containing a 41BB costimulatory domain (e.g., a CAR represented by SEQ ID NO: 1318) when both of them are expressed in human T cells and exposed to target antigen containing cells (e.g., RAJI) for appropriate time interval (e.g., 1-24 hours) under comparable conditions. 
     In one embodiment, a NF-κB activator, including a selective NF-κB activator, is a non-naturally occurring agent and is expressed in the cell exogenously. In one embodiment, the selective NF-κB activator is of viral origin, i.e., it is encoded by a virus or is derived from a virally encoded protein or has a domain of more than 10 amino acid residues (e.g., more than 15 amino acid residues, 20 amino acid residues, 30 amino acid residues or 50 amino acid residues) with more than 80% (e.g., more than 85%, 90%, 95%, or 99%) identity to one or more viral proteins. An exemplary selective NF-κB activator of viral origin is vFLIP K13 (SEQ ID NO:) which is derived from Kaposi&#39;s sarcoma associated herpesvirus. In another embodiment, the selective NF-κB activator is of mammalian or cellular origin. Exemplary selective NF-κB activators of mammalian origin are human NEMO-K277A mutant, human NEMO-K277-deltaV249-K255 mutant, mouse NEMO-K270A mutant, IKK2-5177E-5181E and IKK1-5176E-5180E. In another embodiment, the selective NF-κB activator is of human origin; i.e. it has a domain of more than 10 amino acid residues (e.g., more than 15 amino acid residues, 20 amino acid residues, 30 amino acid residues or 50 amino acid residues) with more than 80% (e.g., more than 85%, 90%, 95%, or 99%) identity to one or more human proteins. In some embodiments, a selective NF-κB activator is composed of two or more fusion proteins (e.g., FKBPx2-NEMO). In some embodiments, the two or more fusion partners of a selective NF-κB activator are each derived from human proteins or have more than 80% identity to the human proteins. 
     In some embodiments, the selective NF-κB activator is encoded by the wild-type nucleic acid sequence while in other embodiments the selective NF-κB activator is encoded by codon-optimized nucleic acid sequence or a mutant sequence. In an exemplary embodiment, vFLIP K13 is encoded by human codon optimized nucleic acid sequence, e.g., K13-opt (SEQ ID NO: 7768). 
     In some embodiments, the immune cells express a single selective NF-κB activator while in other embodiments the immune cells express more than one selective NF-κB activator (e.g., NEMO-K277A plus K13-opt or IKK2-S177E-S181E plus IKK1-S176E-S180E). 
     In some embodiments, the selective NF-κB activator is expressed in an immune cell in a constitutive manner. In other embodiments, the selective NF-κB activator is expressed in an immune cell in an inducible manner. In an exemplary embodiment, inducible expression of a selective NF-κB activator can be achieved through the use of an inducible promoter. Examples of inducible promoters include, but are not limited to a metallothionine inducible promoter, a glucocorticoid inducible promoter, a progesterone inducible promoter, and a tetracycline inducible promoter. RheoSwitch® system represents another transcriptional regulator platform for controlling the expression of a protein. 
     Methods to control the activity of proteins are known in the art and can be used to control the activity of the NF-κB activator, including selective NF-κB activator. In an exemplary embodiment, this involves the expression in the target cell, such as a T cell or an NK cell, of a NEMO or a NEMO mutant fused to a dimerization domain or a switch domain. In an exemplary embodiment, the switch domain comprises of one or more copies of a FKBP12 domain or an FKBP12v36 domain. In some embodiments, the switch domain is attached to the carboxy-terminus of the NF-κB activator (e.g., NEMO) while in other embodiments the switch domain is attached to the amino-terminus of the NF-κB activator (e.g., NEMO). Exposure of target cells expressing such a fusion protein to a suitable dimerizer (e.g., Rimiducid) results in oligomerization of NEMO, which in turn leads to NF-κB activation. In an alternate embodiment, the activity of the selective NF-κB activators can be also controlled by fusing them to the ligand binding domain of a mutated estrogen receptor as has been described (Matta H et al., Journal of Biological Chemistry, 282, 34, 2007). The mutated estrogen receptor does not bind to the physiological ligand estrogen but binds with very high affinity to the synthetic ligand 4-OHT (4-hydroxytamoxifen) and regulates the activity of the fusion partner (e.g., NF-κB activator, e.g., vFLIP K13 or NEMO) in a 4-OHT-dependent fashion. 
     In some embodiments, the selective NF-κB activator is expressed in the immune cells by alteration in its genomic copy using gene editing techniques known in the art. In an exemplary embodiment, a gene editing system (e.g., TALON, Zn finger nuclease or CRISP/Cas9) is used to convert one or both alleles of human NEMO to human NEMO-K277A mutant form. In another exemplary embodiment, a gene editing system is used to convert one or both alleles of human NEMO to human NEMO-K277A-delta-V249-K255 mutant form. The sequence of human NEMO gene targeting constructs that can be used to induce K277A and K277A-delta-V249-K255 mutations are provided in SEQ ID NO: 7771 and 7772, respectively. These sequences can be cloned in a suitable vector (e.g., integration defective lentiviral vector, AAV vector or adenoviral vector). Examples of genomic target sequences for human NEMO for which CRISP/Cas9 gRNAs comprising complementary targeting sequences can be generated are provided in SEQ ID NO: 7759-7762. The gRNA sequences are cloned into the pX330-U6-Chimeric_BB-CBh-hSpCas9 vector (Addgene). Alternatively, the gRNA sequences can be cloned in the pLenti-CRISPR-v2 vector available from Addgene (Plasmid #52961) and following the instructions provided by the distributor. Introduction of the NEMO targeting construct and gRNA encoding constructs into the T cells is carried out essentially as described previously (Knipping F et al, Molecular Therapy: Methods &amp; Clinical Development, Vol 4, 2017). 
     In another or further embodiment of any of the foregoing embodiments described herein, the immune effector cells that express an accessory module encoding a selective NF-κB activator (e.g., hNEMO-K277A, hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, or IKK1-S176E-S180E) show improved in vitro activity (e.g. target antigen induced IL2 production, proliferation, expansion, and delay in terminal differentiation, delay in senescence etc.) against a target antigen expressing cell as compared to a corresponding immune effector cell lacking the accessory module when compared under similar conditions. NF-κB activation in the immune effector cells is measured by using techniques known in the art including, but not limited to, measurement of phosphorylated IxBa, phosphorylated p65, total IκBa, p65 nuclear translocation, upregulation of NF-κB responsive genes, electrophoretic mobility shift assay (EMSA) and NF-κB-based reporter assay etc. In some embodiments, selective NF-κB activation is determined by measuring fold increase in activation of NF-κB in the immune effector cells over the fold increase in activation of AKT pathway. In some embodiments, immune effector cells that express an accessory module encoding a selective NF-κB activator (e.g., K13-opt (human codon optimized K13) or hNEMO-K277A) show higher in vitro activity (e.g. target antigen induced IL2 production, proliferation, expansion, and delay in terminal differentiation, and delay in senescence) towards target antigen expressing cells as compared to the corresponding immune effector cells that lack the expression of an accessory module encoding a selective NF-κB activator (e.g., K13-opt or hNEMO-K277A) when both are tested under similar experimental conditions. In an exemplary embodiments, CD19-CAR-expressing immune effector cells that express an accessory module encoding a selective NF-κB activator (e.g., K13-opt (human codon optimized K13) or hNEMO-K277A) show higher in vitro activity (e.g. target antigen induced IL2 production, proliferation, expansion, and delay in terminal differentiation, and delay in senescence) towards Nalm6 cells as compared to the corresponding CD19-CAR-expressing effector cells that do not express an accessory module encoding a selective NF-κB activator (e.g., K13-opt or hNEMO-K277A) when both are tested under similar experimental conditions. In some embodiments, the in vitro activity (e.g. target antigen induced IL2 production, proliferation, expansion, and delay in terminal differentiation, and delay in senescence) of the immune effector cells that express an accessory module encoding a selective NF-κB activator against the target antigen-expressing cells (i.e. target cells) is at least 5%, 10%, 20%, 30%, 40%, 50% or 100% more than the in vitro activity of a corresponding immune effector cells that do not express an accessory module encoding a selective NF-κB activator. In some embodiments, the in vitro activity (e.g. target antigen induced IL2 production, proliferation, expansion, and delay in terminal differentiation, and delay in senescence) of the immune effector cells that express a selective NF-κB activator (e.g., hNEMO-K277A) against the target antigen-expressing cells (i.e. target cells) is at least 1.25-fold, 1.5-fold, 2-fold, 5-fold or 10-fold more than the in vitro activity of a corresponding immune effector cells that lack the expression of the selective NF-κB activator. In an embodiment, the immune effector T cells (e.g., CD19-CAR-T cells) that express a selective NF-κB activator produce at least 5%, 10%, 20%, 30%, 40%, 50% or 100% more IL2 when exposed to a target antigen expressing cell (e.g., Nalm-6 cells) as compared to the control immune effector T cells (e.g., CD19-CAR-T cells) that lack the expression of the selective NF-κB activator. In an embodiment, the immune effector T cells (e.g., CD19-CAR-T cells) that express a selective NF-κB activator show at least 5%, 10%, 20%, 30%, 40%, 50% or 100% more proliferation when exposed to a target antigen expressing cell (e.g., Nalm-6 cells) as compared to the control immune effector T cells (e.g., CAR-T cells) that lack the expression of the selective NF-κB activator. In an embodiment, the immune effector T cells (e.g., CD19-CAR-T cells) that express a selective NF-κB activator show at least 5%, 10%, 20%, 30%, 40%, 50% or 100% less markers of exhaustion when exposed to a target antigen expressing cell (e.g., Nalm-6 cells) as compared to the control immune effector T cells (e.g., CAR-T cells) that lack the expression of the selective NF-κB activator. In an embodiment, the immune effector T cells (e.g., CD19-CAR-T cells) that express a selective NF-κB activator show at least 5%, 10%, 20%, 30%, 40%, 50% or 100% less markers of terminal differentiation when exposed to a target antigen expressing cell (e.g., Nalm-6 cells) as compared to the control immune effector T cells (e.g., CAR-T cells) that lack the expression of the selective NF-κB activator. In an embodiment, the immune effector T cells (e.g., CD19-CAR-T cells) that express a selective NF-κB activator show at least 5%, 10%, 20%, 30%, 40%, 50% or 100% more cytotoxicity when serially exposed to target antigen expressing cells (e.g., Nalm-6 cells) over a period of 3-4 weeks as compared to the control immune effector T cells (e.g., CAR-T cells) that lack the expression of the selective NF-κB activator. In some embodiments, the immune effector cell that express an accessory module encoding a selective NF-κB activator is a T cell (e.g., a CD8 T cell, a CD4 T cell, a CAR-T cell, a TIL, a TREG cell, an NKT cell), a NK cell (e.g., a CAR-NK cell), a macrophage (e.g., a CAR-expressing macrophage), an antigen presenting cell (e.g., a dendritic cell), a stem cell, an induced pluripotent stem cell (iPSC) or a stem cell that can give rise to an immune effector cell. 
     In another or further embodiment of any of the foregoing embodiments described herein, the immune effector cells that express an accessory module encoding a selective NF-κB activator, show higher in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a luciferase expressing tumor or animal survival) against a target antigen expressing cell as compared to control immune effector cells that do not express the accessory module encoding a selective NF-κB activator when both are tested under similar conditions. NF-κB activation in the immune effector cells is measured by using techniques known in the art including, but not limited to, measurement of phosphorylated IκBa, total IκBα, p65 nuclear translocation, upregulation of NF-κB responsive genes, electrophoretic mobility shift assay (EMSA) and NF-κB-based reporter assay etc. In some embodiments, selective NF-κB activation is determined by measuring fold increase in activation of NF-κB in the immune effector cells over the fold increase in activation of AKT pathway. For example, in some embodiments, CD19-CAR-expressing immune effector cells that express an accessory module encoding a selective NF-κB activator (e.g., K13-opt (human codon optimized K13) or hNEMO-K277A) show higher in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a FLuc expressing tumor or animal survival) towards Nalm6-FLuc cells in an NSG mouse xenograft model as compared to the corresponding CD19-CAR-expressing effector cells that lack an accessory module encoding a selective NF-κB activator (e.g., K13-opt (human codon optimized K13) or hNEMO-K277A) when tested under similar experimental conditions. In some embodiments, the in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a FLuc expressing tumor or animal survival) of the immune effector cells (e.g., CD19-CAR-T cells) that express an accessory module encoding a selective NF-κB activator against the target antigen-expressing cells (e.g., Nalm-6) in a NSG mouse xenograft model is at least 5, 10, 20, 30, 40, 50% or 100% more than the in vivo activity of a corresponding immune effector cells that lack an accessory module encoding a selective NF-κB activator. In some embodiments, the in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a FLuc expressing tumor or animal survival) of the immune effector cells (e.g., CD19-CAR-T cells) that encode an accessory module encoding a selective NF-κB activator against the target antigen-expressing cells (e.g., Nalm6) in a NSG mouse xenograft model is at least 1.25-fold, 1.5-fold, 2-fold, 5-fold or 10-fold more than the in vivo activity of a corresponding immune effector cells that lack the expression of an accessory module encoding a selective NF-κB activator. In some embodiments, the immune effector cell expressing an accessory module encoding a selective NF-κB activator is a T cell (e.g., a CD8 T cell, a CD4 T cell, a CAR-T cell, a TIL, a TREG cell, an NKT cell), a NK cell (e.g., a CAR-NK cell), a macrophage (e.g., a CAR-expressing macrophage), an antigen presenting cell (e.g., a dendritic cell), a stem cell, an induced pluripotent stem cell (iPSC) or a stem cell that can give rise to an immune effector cell. 
     In another or further embodiment of any of the foregoing embodiments described herein, the immune effector cells expressing the accessory module, e.g., hNEMO-K277A, hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, IKK1-S176E-S180E, or MYD88-L265P show higher in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a FLuc expressing tumor or animal survival) against a target antigen expressing cell as compared to a corresponding immune effector cell lacking the accessory module when compared under similar conditions. For example, in some embodiments, CD19-CAR-expressing immune effector cells that also co-expresses hNEMO-K277A, hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, IKK1-S176E-S180E, or MYD88-L265P show higher in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a FLuc expressing tumor or animal survival) towards Nalm6-FLuc cells in an NSG mouse xenograft model as compared to the corresponding CD19-CAR-expressing effector cells that lack hNEMO-K277A expression when tested under similar experimental conditions. In some embodiments, the in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a FLuc expressing tumor or animal survival) of the immune effector cells expressing the accessory module described herein (e.g., hNEMO-K277A, hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, IKK1-S176E-S180E, or MYD88-L265P) against the target antigen-expressing cells (i.e. target cells) in a NSG mouse xenograft model is at least 5, 10, 20, 30, 40, 50% or 100% more than the in vivo activity of a corresponding immune effector cell that lacks the expression of the accessory module. In some embodiments, the in vivo activity (e.g. in vivo expansion, in vivo persistence, tumor reduction, reduction in bioluminescence value obtained from a FLuc expressing tumor or animal survival) of the immune effector cells expressing the accessory module described herein (e.g., hNEMO-K277A, hNEMO-K277A-deltaV249-K555, mNEMO-K270A, K13-opt, IKK2-S177E-S181E, IKK1-S176E-S180E, or MYD88-L265P) against the target antigen-expressing cells (i.e. target cells) in a NSG mouse xenograft model is at least 1.25-fold, 1.5-fold, 2-fold, 5-fold or 10-fold more than the in vivo activity of a corresponding immune effector cell that lacks the expression of the accessory module. In some embodiments, the accessory module-expressing effector cell is a T cell (e.g., a CD8 T cell, a CD4 T cell, a CAR-T cell, a TIL, a TREG cell, an NKT cell), a NK cell (e.g., a CAR-NK cell), a macrophage (e.g., a CAR-expressing macrophage), an antigen presenting cell (e.g., a dendritic cell), an induced pluripotent stem cell (iPSC) or a stem cell that can give rise to an immune effector cell. 
     The disclosure further provides that expression of a selective NF-κB activator can be used to improve the cytokine secretion, antigen presentation and immune response generated by antigen presenting cells, including dendritic cells. The disclosure further provides a method of improving the efficacy of vaccine, including cancer vaccines, by expression of a selective NF-κB activator in the antigen presenting cells ex vivo or in vivo. In one embodiment, the use of selective NF-κB activators increase cytokine production (e.g., TNFa) by antigen presenting cells (e.g., dendritic cells) by more than at least 15%. 
     The disclosure further provides that an accessory module encoding CMV-141 (SEQ ID NO: 7770) can be expressed in the immune effector cells, e.g., T cells, e.g., CAR-T cells or TCR-T cells, to delay their exhaustion and improve their long term persistence. The CMV-141 can be expressed in immune effector cells in an inducible or constitutive manner. 
     In some embodiments, cells, e.g., T or NKT or stem cells or iPSC or synthetic T cell, are generated that express a non-naturally occurring immune receptor, e.g., CAR, and/or an NF-κB stimulatory molecule described herein by using a combination of gene insertion using the SBTS and genetic editing using a nuclease (e.g., Zinc finger nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), the CRISPR/Cas system, or engineered meganuclease reengineered homing endonucleases). 
     In another embodiment, the disclosure provides a method of making a cell (e.g., an immune effector cell or population thereof) comprising introducing into (e.g., transducing) a cell, e.g., a T cell, a NKT cell or a stem cell or a iPSC or a synthetic T cell described herein, with a vector comprising a nucleic acid encoding a non-naturally occurring immune receptor, e.g., CAR, and/or an NF-κB stimulatory molecule. 
     In various embodiments, the cells for modifications with a non-natural immune receptor and/or NF-κB stimulatory molecule described herein, including T cells or NK cells may be obtained from a subject desiring therapy. T cells can be obtained from a number of sources, including peripheral blood mononuclear cells, bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, and tumors. T cells could be tissue resident gamma-delta T cells, which can be cultured and expanded in vitro prior to expression of the non-naturally occurring immune receptor, e.g., CAR, and/or NF-κB stimulatory molecule. 
     In one embodiment, the disclosure provides a number of chimeric antigen receptors (CAR) comprising an antigen binding domain (e.g., antibody or antibody fragment, TCR or TCR fragment) engineered for specific binding to a disease-associated antigen, e.g., a tumor antigen described herein. In one embodiment, the disclosure provides an immune effector cell (e.g., T cell, NK cell) engineered to express a non-naturally occurring immune receptor (e.g., a CAR or a recombinant TCR) and/or NF-κB stimulatory molecule, wherein the engineered immune effector cell exhibits a therapeutic property. In one embodiment, the disclosure provides an immune effector cell (e.g., T cell, NK cell) engineered to express a non-naturally occurring immune receptor (e.g., a CAR or a recombinant TCR) and/or NF-κB stimulatory molecule, wherein the engineered immune effector cell exhibits anticancer or anti-infection (e.g., anti-HIV-1) property. In some embodiments, the NF-κB stimulatory molecule may be expressed in a T cell (e.g. a Tumor infiltrating lymphocyte or TIL) with its endogenous TCR, wherein the the engineered immune effector cell exhibits anticancer or anti-infection (e.g., anti-HIV-1) property. In one embodiment, a cell is transformed with the non-naturally occurring immune receptor (e.g., a CAR or a recombinant TCR) and an NF-κB stimulatory molecule and the non-naturally occurring immune receptor is expressed on the cell surface. In some embodiments, the cell (e.g., T cell, NK cell) is transduced with a viral vector encoding a non-naturally occurring immune receptor (e.g., a CAR or a recombinant TCR) and/or NF-κB stimulatory molecule. In some embodiments, the viral vector is a retroviral vector. In some embodiments, the viral vector is a lentiviral vector. In some such embodiments, the cell may stably express the non-naturally occurring immune receptor (e.g., a CAR or a recombinant TCR) and/or NF-κB stimulatory molecule. In another embodiment, the cell (e.g., T cell, NK cell) is transfected with a nucleic acid, e.g., mRNA, cDNA, DNA, encoding a non-naturally occurring immune receptor (e.g., a CAR or a recombinant TCR) and/or NF-κB stimulatory molecule. In some such embodiments, the cell may transiently express the non-naturally occurring immune receptor (e.g., a CAR or a recombinant TCR) and/or NF-κB stimulatory molecule. In some embodiments, the NF-κB stimulatory molecule may be expressed in a T cell (e.g. a Tumor infiltrating lymphocyte or TIL) with its endogenous TCR. 
     The disclosure provides immune effector cells (e.g., T cells, NK cells) that are engineered to contain one or more non-naturally occurring immune receptors (e.g., CARs/TCRs) and/or NF-κB stimulatory molecules that direct the immune effector cells to diseased cells or disease-associated cells, such as cancer cells. This is achieved through an antigen binding domain on the immune receptor that is specific for a cancer associated antigen. There are two classes of cancer associated antigens (tumor antigens) that can be targeted by the CARs of the disclosure: (1) cancer associated antigens that are expressed on the surface of cancer cells; and (2) cancer associated antigens that itself is intracellular, however, a fragment of such antigen (peptide) is presented on the surface of the cancer cells by MHC (major histocompatibility complex). The disclosure also provides immune effector cells (e.g., T cells, NK cells) that contain endogenous TCRs and/or engineered to express one or more NF-κB stimulatory molecules that direct the immune effector cells to diseased cells or disease-associated cells, such as cancer cells. 
     Furthermore, the disclosure provides CARs, TCRs and CAR/TCR-expressing cells that also express an NF-κB stimulatory molecule and their use in medicaments or methods for treating, among other diseases, cancer or any malignancy or autoimmune diseases or infectious disease or degenerative disease or allergic disease involving cells or tissues which express a tumor antigen or disease associated antigen as described herein. 
     In one embodiment, the disclosure provides an immune effector cell (e.g., T cell, NK cell) engineered to express a non-naturally occurring immune receptor, e.g., CAR and/or TCR, and an NF-κB stimulatory molecule, wherein the engineered immune effector cell exhibits an anti-disease property, such as antitumor property. One type of antigen is a cancer associated antigen (i.e., tumor antigen) described herein. In one aspect, the antigen binding domain of the non-naturally occurring immune receptor, e.g., CAR, comprises a partially humanized antibody fragment. In one embodiment, the antigen binding domain of the non-naturally occurring immune receptor, e.g., CAR, comprises a partially humanized scFv. Accordingly, the disclosure provides non-naturally occurring immune receptors, e.g., CARs, that comprises a humanized antigen binding domain and is engineered into a cell, e.g., a T cell or a NK cell, wherein the cell also expresses an NF-κB stimulatory molecule and methods of their use for adoptive therapy. 
     In one embodiment, the disclosure provides an immune effector cell (e.g., T cell, NK cell) with its endogenous immune receptor (e.g. a TCR) that is engineered to express an NF-κB stimulatory molecule, wherein the engineered immune effector cell exhibits an anti-disease property, such as antitumor property or anti-HIV-1 property. 
     Further provided herein are genetically engineered cells, comprising the polynucleotides and/or the non-naturally occurring immune receptors described herein. In some embodiments, the cell is a T-lymphocyte (T-cell). In some embodiment the cell is a naïve T cells, a central memory T cells, an effector memory T cell, a regulatory T cell (Treg) or a combination thereof. In some embodiments, the cell is a natural killer (NK) cell, a hematopoietic stem cell (HSC), an embryonic stem cell, or a pluripotent stem cell. Genetically engineered cells which may comprise and express the non-naturally occurring immune receptors (e.g., CARs and/or TCRs) of the disclosure in combination with an NF-κB stimulatory molecule, include, but are not limited to, T-lymphocytes (T-cells), naïve T cells (TN), memory T cells (for example, central memory T cells (TCM), effector memory cells (TEM)), natural killer cells, hematopoietic stem cells and/or pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny. In an embodiment, the genetically engineered cells are autologous cells. In an embodiment, the genetically engineered cells are allogeneic cells. By way of example, individual T-cells of the invention may be CD4+/CD8-, CD4-/CD8+, CD4-/CD8- or CD4+/CD8+. The T-cells may be a mixed population of CD4+/CD8- and CD4-/CD8+ cells or a population of a single clone. CD4+ T-cells of the invention may produce IL-2, IFNγ, TNFa and other T-cell effector cytokines when co-cultured in vitro with cells expressing the target antigens (for example CD20+ and/or CD19+ tumor cells). CD8+ T-cells of the invention may lyse antigen-specific target cells when co-cultured in vitro with the target cells. In some embodiments, T cells may be any one or more of CD45RA+ CD62L+ naïve cells, CD45RO+ CD62L+ central memory cells, CD62L-effector memory cells or a combination thereof (Berger et al., Adoptive transfer of virus-specific and tumor-specific T cell immunity.  Curr Opin Immunol  2009 21(2)224-232). Genetically modified cells may be produced by stably transfecting cells with DNA encoding the non-naturally occurring immune receptors (e.g., CARs and/or TCRs) and/or NFκB stimulatory molecule of the disclosure. The transfected cells demonstrating presence of a single integrated un-rearranged vector and expression of the non-naturally occurring immune receptors (e.g., CARs and/or TCRs) and/or NF-κB stimulatory molecule may be expanded ex vivo. In one embodiment, the cells selected for ex vivo expansion are CD8+ and demonstrates the capacity to specifically recognize and lyse antigen-specific target cells. 
     Stimulation of the T-cells by an antigen under proper conditions results in proliferation (expansion) of the cells and/or production of IL-2. The cells comprising the non-naturally occurring immune receptors (e.g., CARs and/or TCRs) and/or NF-κB stimulatory molecule of the disclosure will expand in number in response to the binding of one or more antigens to the antigen-specific targeting regions of the non-naturally occurring immune receptors (e.g., CARs and/or TCRs). The disclosure also provides a method of making and expanding cells expressing a non-naturally occurring immune receptor (e.g., CAR and/or TCR). The method comprises transfecting or transducing the cells with the vector(s) expressing the non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule and stimulating the cells with cells expressing the target antigens, recombinant target antigens, or an antibody to the receptor to cause the cells to proliferate, so as to make and expand T-cells. In an embodiment, the cells may be any one or more of T-lymphocytes (T-cells), natural killer (NK) cells, hematopoietic stem cells (HSCs) or pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny. In an embodiment, the NF-κB stimulatory molecule can be expressed in the cells (e.g., T cells, NK cells, or stem cell that can give rise to immune cells) without the introduction of the non-naturally occurring immune receptors (e.g., CARs and/or TCRs). 
     Immune effector cells such as T cells and NK cells comprising non-naturally occurring immune receptors (e.g., CARs and/or TCRs) and/or NF-κB stimulatory molecule as described herein may be activated and expanded generally using methods as described, for example, in U.S. Pat. Nos. 6,352,694; 6,534,055; 6,905,680; 6,692,964; 5,858,358; 6,887,466; 6,905,681; 7,144,575; 7,067,318; 7,172,869; 7,232,566; 7,175,843; 5,883,223; 6,905,874; 6,797,514; 6,867,041; and U.S. Patent Application Publication No. 20060121005. 
     In one embodiment, the genetically engineered cells comprise nucleic acid molecules encoding conventional CARs 1 to 6 or conventional CARs 1 to 6 which are part of the backbones described herein, such as backbone-1, backbone-2, backbone-13, backbone-14, backbone-37, backbone-38, backbone-49, backbone-50, backbone-60 or backbone-61, and an NF-κB stimulatory molecule wherein the antigen-specific domain of the CARs is specific to MPL, CD19, CD20, BCMA, CD22, CD30, CD33, CD123, CD138, CLL1, TCR-beta 1 constant chain, TCR-beta2 constant chain, TCRgamma/delta, mesothelin, IL13Ra2, ALK, PTK7, DLL3, TROP2, Timl, LAMP1, CS1, Lyml, Lym2, TSHR, NY-ESO-1/MHC class 1 complex, WT1/MHC class I complex, Ras/MHC class I complex, AFP/MHC class I complex, HPV-E6/MHC class I complex, HPV-E7/MHC class I complex, CD179a, CLD18A2, CD43 epitope, or HIV1 env protein gp120. 
     In one embodiment, the cell is a T cell and the T cell is deficient in one or more of endogenous T cell receptor chains. T cells stably lacking expression of a functional TCR according to the disclosure may be produced using a, variety of approaches such as use of Zn finger nucleases (ZFN), CRISP/Cas9 and shRNA targeting the endogenous T cell receptor chains. A non-limiting exemplary method relating to shRNAs is described in US 2012/0321667A1, which is incorporated herein by reference. Another non-limitng expemplary method relating to eliminating endogenous TCR expression using ZFNs targeting constant regions of a and 13 chains of TCRs is described in Torikai H et al. (Blood, 119(24), June, 14 2012). 
     A T cell lacking a functional endogenous TCR can be, e.g., engineered such that it does not express any functional endogenous TCR on its surface, engineered such that it does not express one or more subunits (e.g. constant chains of endogenous TCRα, TCRβ1, TCRβ2, TCRγ, TCRδ or pre-TCRα) that comprise a functional endogenous TCR or engineered such that it produces very little functional endogenous TCR on its surface. Alternatively, the T cell can express a substantially impaired endogenous TCR, e.g., by expression of mutated or truncated forms of one or more of the subunits of the TCR. The term “substantially impaired TCR” means that this TCR will not elicit an adverse immune reaction in a host. In yet a further alternative a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule can be cloned into a TCR loci in at T cell genome and thus the non-naturally occurring immune receptors (e.g., CARs and/or TCRs) and/or NF-κB stimulatory molecule would be under the control of the endogenous T cell expression system. 
     The disclosure demonstrates that in contrast to the situation with the Pt or the 2 nd  generation CAR constructs, TFPs based on CD3ε, CD3γ, and CD3δ chains (designated as CD3ε/γ/δ TFPs) have poor expression and activity when expressed in αβ T cells that lack or have impaired functional endogenous or native TCRα chain polypeptide on their surface. For example, it is observed that CD3ε/γ/δ TFPs have impaired expression and activity (e.g., T cell activation, proliferation, cytokine production and cytotoxicity etc.) in αβ T cell in which the endogenous TRAC genomic locus has been disrupted by the TFP expression cassette. The disclosure provides a solution to this problem by re-expressing a TCRα constant chain (TRAC chain) polypeptide or a fragment thereof in T cells in which the expression of native full length TCRα chain polypeptide has been reduced or eliminated. In an embodiment, the re-expressed TCRα constant chain polypeptide or TCRα constant chain fragment allows the reconstitution of a functional CD3ε/γ/δ TFP-TCR-CD3 signaling complex in a αβ T cell in which the expression of the native TCRα constant chain is impaired, reduced or eliminated. In an embodiment, the re-expressed TCRα constant chain or TCRα constant chain fragment improves by more than 15% (e.g., more than 20%, 50%, 75%, or 100% etc.) target antigen-induced cytokine (e.g., IL2, TNFα, IFNγ) production, proliferation and/or cytotoxic activity of CD3ε/γ/δ TFP-expressing αβ T cell in which the expression of the native TCRα constant chain is impaired, reduced or eliminated. In an embodiment, the re-expressed TCRα constant chain or TCRα constant chain fragment allows enhanced expression of the CD3ε/γ/δ TFP in a αβ T cell in which the expression of the native TCRα constant chain is impaired, reduced or eliminated. In an embodiment, the re-expressed TCRα constant chain or TCRα constant chain fragment allows more than 15% (e.g., more than 20%, 50%, 75%, or 100% etc.) increase in expression of the CD3ε/γ/δ TFP in a αβ T cell in which the expression of the native TCRa constant chain is impaired, reduced or eliminated. In an exemplary embodiment, the expression and signaling activity of CD3ε/γ/δ TFPs can be restored in αβ T cells in which the expression of native TCRα chain is reduced or eliminated by introducing into such T cells a nucleic acid construct encoding an exogenous TCRα constant chain (TRAC chain) (e.g., SEQ ID NO: 1010). In a preferred embodiment, the nucleotide sequence encoding the exogenous TRAC chain is codon optimized and differs from the endogenous or native TCRα constant chain in its nucleotide sequence. In an alternate embodiment, the nucleotide sequence encoding the exogenous TRAC chain is codon optimized and carries one or more amino acid substitutions that are known to enhance the expression of human TCRα constant chain (see Table 3). In an exemplary embodiment, the exogenous TRAC chains that can be used to allow re-expression and/or activity of TFP-TCR-CD3 complex in αβ T cells in which the expression of endogenous TCRα gene has been down-regulated or eliminated have sequence as shown in SEQ ID NO: 3886 to 3894 or have sequences which encode for polypeptides with greater than 80% homology to the polypeptides encoded by sequences shown in SEQ ID NO: 3886 to 3894. To enable its cell surface expression, the nucleotide sequence encoding the exogenous TCRα constant chain (TRAC) is operationally linked to nucleotide sequence encoding a signal peptide. In an embodiment, additional non-natuarally occuring sequences (e.g., linkers or antigen binding domain) may be optionally added to the sequence encoding the TRAC chain as long as they do not interfere with its ability to recruit other components of the TCR-CD3 signaling complex and/or CD3ε/γ/δ TFP. In an embodiment, the exogenous TCRα constant chain polypeptide is not operationally linked to the native Va sequence (i.e. antigen binding domain) present in the T cell in which it is expressed. In an embodiment, the expression of exogenous TCRα constant chain polypeptide does not allow the αβ T cell to regain its native antigen recognition specificity and/or affinity, e.g., to recognize the MHC-peptide antigen complex which was recognized by the the T cell with its endogenous TCRa chain. In an exemplary embodiment, the accessory module encoding an exogenous TCRa constant chain can be expressed in αβ T cells either by itself (SEQ ID NO: 1010) using an appropriate method (e.g., lentiviral mediated gene transfer) or it can be co-expressed with the TFP expression cassettes using a single vector (e.g. a lentiviral vector). Alternate methods of delivery and expression of two or more genes or RNAs are known in the art and described in this disclosure and can be used in the alternate embodiments of the invention. The nucleotide sequence of exemplary constructs coexpressing a TCRα constant chain with CD3ε/γ/δ TFP constructs targeting MPL are shown in SEQ ID NOs: 3538, 3540, and 3542. In the exemplary construct CD8SP-MPL-Hu-161-2-(vL-vH)-CD3e-ECDTMCP-opt2-F-P2A-IgSP4-[TRAC-opt2] (SEQ ID NO: 3538), the first cassette encodes a CD3E-TFP comprising a CD8 signal peptide followed by a humanized scFV targeting the human MPL protein and extracellular, transmembrane and cytosolic domain of CD3E. This TFP encoding cassette is followed in frame by a linker encoding Furine-SGSG-P2A and a cassette encoding a signal peptide (IgSP) and a codon optimized nucleotide sequence encoding TRAC. In an exemplary embodiment, the entire cassette can be expressed in αβ T cells lacking endogenous TCRa chain using a lentiviral vector. 
     In an alternate embodiment, the expression of TCRα constant chain polypeptide can be restored in αβ T cells that lack or have impaired functional endogenous or native TCRα chain polypeptide on their surface by using the endogenous TCRα constant chain gene. In an exemplary embodiment, the expression of TCRα constant chain polypeptide can be restored in αβ T cells that lack or have impaired functional endogenous or native TCRα chain polypeptide on their surface by functionally linking in frame a nucleic acid sequence encoding a signal peptide to at least one copy of the endogenous TCRα constant chain gene using techniques of gene editing known in the art. In an exemplary embodiment, the nucleic acid sequence encoding a signal peptide is operationally linked in frame to the first exon of at least one of the endogenous TCRα constant chain genes so as to allow the expression of a TCRα constant chain polypeptide on the surface of the T cells. In an embodiment, the expression cassette encoding the signal peptide and TCRα constant chain gene is under the transcriptional regulatory control of the endogenous TCRα promoter. In an embodiment, the expression cassette encoding the signal peptide and TCRα constant chain gene shares the 3′ untranslated sequence and regulatory control of the endogenous TCRα gene. In an alternate embodiment, the expression cassette encoding the signal peptide and TCRα constant chain gene is under an exogenous promoter (e.g., EF1α or CMV promoter). 
     In an exemplary embodiment, expression of TCRα constant chain polypeptide can be restored in αβ T cells in which the endogenous or the native TCRα chain gene has been disrupted by targeted integration of a cassette encoding a TFP by designing the targeting cassette such that TFP cassette is followed in frame by a 2A cleavable linker, a signal peptide (e.g., a CD8 signal peptide or an IgH signal peptide) and the first exon of the TCRα constant chain (TRAC) ( FIG.  5 C ). An exemplary such targeting construct is represented by SEQ ID NO: 3860. In this embodiment, the TCRα constant chain is expressed from the endogenous TCRα constatnt chain (TRAC) gene whose cell surface expression is facilitated by the signal peptide present in the targeting cassette. In this embodiment, the TCRα constant chain is expressed under the regulatory control of the TCRα gene promoter and TCRα 3′ untranslataed region. An alternate exemplary targeting construct is represented by SEQ ID NO: 3859 and can be used in alternate embodiments of the disclosure to disrupt the endogenous TCRα chain by targeting integration of a cassette encoding a TFP while simultaneously allowing re-expression of a TCRα constant chain from an expression cassette encoding a signal peptide followed by a codon optimized TCRα constant chain cDNA and a polyA sequence ( FIG.  5 B ). 
     The disclosure also demonstrates that in contrast to the situation with the 1St or the 2 nd  generation CAR constructs, CD3ε/γ/δ TFPs lose their activity when expressed in αβ T cells (i.e. T cells expressing TCRα and TCRβ chains) that lack or have impaired functional endogenous or native TCRβ1 and TCRβ2 chain polypeptides on their surface. For example, the disclosure provides that CD3ε/γ/δ TFPs have impaired expression and activity (e.g., T cell activation, proliferation, cytokine production and cytotoxicity etc.) in αβ T cells in which the endogenous TCRβ1 and TCRβ2 genomic loci have been disrupted. The disclosure provides a solution to this problem by re-expressing TCRβ1 or TCRβ2 constant chain polypeptides or a fragment thereof in T cells in which the expression of native full length TCRβ1 and TCRβ2 chain polypeptides have been reduced or eliminated. In an embodiment, the re-expressed TCRβ1/(32 constant chain polypeptide or TCRβ1/(32 constant chain fragment allows the reconstitution of a functional TFP-TCR-CD3 signaling complex in a T cell, e.g., a αβ T cell, in which the expression of the native TCRβ1 and/or (32 constant chain is impaired, reduced or eliminated. In an embodiment, the re-expressed TCRβ1/(32 constant chain or TCRβ1/(32 constant chain fragment improves by more than 15% (e.g., more than 20%, 50%, 75%, or 100% etc.) target antigen-induced cytokine (e.g., IL2, TNFα, IFNγ) production, proliferation and/or cytotoxic activity of TFP-expressing αβ T cell in which the expression of the native TCRβ1 and/or (32 constant chain is impaired, reduced or eliminated. In an embodiment, the re-expressed TCRβ1/(32 constant chain or TCRβ1/(32 constant chain fragment allows enhanced expression of the CD3ε/γ/δ TFP in a αβ T cell in which the expression of the native TCRβ1 and/or TCRβ2 constant chains is impaired, reduced or eliminated. In an embodiment, the re-expressed TCRβ1/(32 constant chain or TCRβ1/(32 constant chain fragment allows more than 15% (e.g., more than 20%, 50%, 75%, or 100% etc.) increase in expression of the CD3ε/γ/δ TFP in a αβ T cell in which the expression of the native TCRβ1 and/or TCRβ2 constant chain is impaired, reduced or eliminated. In an exemplary embodiment, the expression and signaling activity of CD3ε/γ/δ TFPs can be restored in T cells in which the expression of native TCRβ1 and/or TCRβ2 chain is reduced or eliminated by introducing into such T cells a nucleic acid construct encoding an exogenous TCRβ1/(32 constant chain (TRBC chain) (e.g., SEQ ID NO: 1011). In a preferred embodiment, the nucleotide sequence encoding the exogenous TCRβ1/(32 constant chain is codon optimized and differs from the endogenous or native TCRβ1 and TCRβ2 constant chains in its nucleotide sequence. In an alternate embodiment, the nucleotide sequence encoding the exogenous TCRβ1/(32 constant chain is codon optimized and carries one or more amino acid substitutions that are known to enhance the expression of human TCRβ1/(32 constant chain (see Table 4a, 4b). In an exemplary embodiment, the exogenous TCRβ1/(32 chains that can be used to allow re-expression and/or activity of TFP-TCR-CD3 complex in T cells in which the expression of endogenous TCRβ1 and (32 chains has been down-regulated or eliminated have sequence as shown in SEQ ID NO: 3895 to 3900 or have sequences which encode for polypeptides with greater than 80% homology to the polypeptides encoded by sequences shown in SEQ ID NO: 3895 to 3900. To enable its cell surface expression, the nucleotide sequence encoding the exogenous TCRβ1/(32 constant chain (TRBC) is operationally linked to nucleotide sequence encoding a signal peptide. In an embodiment, additional non-natuarally occuring sequences (e.g., linkers or antigen binding domain) may be optionally added to the sequence encoding the TCRβ1/(32 constant chain (TRBC) as long as they do not interfere with its ability to recruit other components of the TCR-CD3 signaling complex and/or TFP. In an embodiment, the exogenous TCRβ1/(32 constant chain polypeptide is not operationally linked to the native VP sequence (i.e. antigen binding domain) present in the T cell in which it is expressed. In an embodiment, the expression of exogenous TCRβ1/(32 constant chain polypeptide does not allow the T cell to regain its native antigen recognition specificity and/or affinity, e.g., to recognize the MHC-peptide antigen complex which was recognized by the the T cell with its endogenous TCRβ1/(32 chain. In an exemplary embodiment, the accessory module encoding the exogenous TCRβ1/(32 constant chain can be expressed in T cells either by itself (e.g., SEQ ID NO: 1011) using an appropriate method (e.g., lentiviral mediated gene transfer) or it can be co-expressed with the CD3ε/γ/δ TFP expression cassettes using a single vector (e.g. a lentiviral vector). Alternate methods of delivery and expression of two or more genes or RNAs are known in the art and described in this disclosure and can be used in the alternate embodiments of the disclosure. The nucleotide sequence of exemplary constructs coexpressing a TCRβ constant chain with TFP constructs targeting MPL are shown in SEQ ID NOs: 3537, 3539, and 3541. In the exemplary construct CD8SP-MPL-Hu-161-2-(vL-vH)-CD3e-ECDTMCP-opt2-F-P2A-IgSP4-[TRBC-opt2] (SEQ ID NO: 3537), the first cassette encodes a TFP comprising a CD8 signal peptide followed by a humanized scFV targeting the human MPL protein and extracellular, transmembrane and cytosolic domain of CD3E. This TFP encoding cassette is followed in frame by a linker encoding Furine-SGSG-P2A and a cassette encoding a signal peptide (IgSP) and a codon optimized nucleotide sequence encoding a TCRβ constant chain (TRBC). In an exemplary embodiment, the entire cassette can be expressed in T cells lacking endogenous TCRβ chain using a lentiviral vector. 
     In an alternate embodiment, the expression of TCRβ1 or (32 constant chain polypeptide can be restored in αβ T cells that lack or have impaired functional endogenous or native TCRα chain polypeptide on their surface by using the endogenous TCRβ1 or (32 constant chain gene. In an exemplary embodiment, the expression of TCRβ1/(32 constant chain polypeptide and the co-expressed TFP can be restored in αβ T cells that lack or have impaired functional endogenous or native TCRβ chain polypeptide on their surface by operationally linking in frame a nucleic acid sequence encoding a signal peptide to at least one copy of the endogenous TCRβ1 or TCRβ2 constant chain gene using techniques of gene editing known in the art. In an exemplary embodiment, the nucleic acid sequence encoding a signal peptide is operationally linked in frame to the first exon of at least one of the endogenous TCRβ1 or TCRβ2 constant chain genes so as to allow the expression of a TCRβ1/(32 constant chain polypeptide and the coexpressed TFP on the surface of the T cells. In an embodiment, the expression cassette encoding the signal peptide and TCRβ1/(32 constant chain is under the transcriptional regulatory control of the endogenous TCRβ1/(32 promoter. In an embodiment, the expression cassette encoding the signal peptide and TCRβ1/(32 constant chain is under the 3′ untranslated sequence and regulatory control of the endogenous TCRβ1/(32 gene. In an alternate embodiment, the expression cassette encoding the signal peptide and TCRβ1/(32 constant chain is under an exogenous promoter (e.g., EFla or CMV promoter). 
     In an exemplary embodiment, expression of TCRβ1/132 constant chain polypeptide can be restored in αβ T cells in which the endogenous or the native TCRβ1 and TCRβ2 chain genes have been disrupted by targeted integration of cassettes encoding a TFP by designing the targeting cassette such that TFP cassette is followed in frame by a 2A cleavable linker, a signal peptide (e.g., a CD8 signal peptide or an IgH signal peptide) and the first exon of the TCRβ1/(32 constant chain (TRBC). 
     It has been observed that directing the CAR cassette to the TRAC locus result in approximately 95% T cells becoming TCR negative. Such TCR-negative T cells could be used in an allogeneic setting as they are less likely to cause graft vs host disease (GVHD). However, re-expression of TRAC chain in T cells in which the TRAC locus has been targeted by a TFP cassette would potentially lead to expression of the full length TCRβ chain including the VP region. Such T cells, even though lacking the MHC recognition provided by Va region, would be potentially able to recognize allo-antigens presented by MHC complex through their TCRβ chains and therefore potentially cause GVHD. In alternate embodiments of the disclosure, both TCRα and TCRβ1 or (32 chains are re-expressed in CD3ε/γ/δ TFP-expressing αβ T cells in which the expression of endogenous TCRα and TCRβ1 and TCRβ2 chains have been down-regulated or eliminated. 
     In the above example, an exogenous TRAC or TRBC is coexpressed with a TFP-expressing construct to restore the expression and/or activity of CD3ε/γ/δ TFP in α/β T cells in which the expression of endogenous TCRα and/or TCRβ chains have been down-regulated or eliminated by, for example, targeting of their genomic loci. In an alternate embodiment of the invention, expression of exogenous TCRα and/or TCRβ1/(32 constant chains is used to restore TCR/CD3 complex expression in any α/β T cell, including a wild-type α/β T cell or an α/βT cell expressing a chimeric antigen receptor, a chimeric T cell receptor (cTCR), an AbTCR, or a synthetic immune receptor. Finally, a similar approach can be used to restore CAR/TFP and/or TCR/CD3 expression in γ/δ T cells in which the expression of endogenous TCRγ and/or TCR chains have been down-regulated or eliminated. Exemplary constant chains of TCRγ (TRGC) and TCR (TRDC) that can be expressed in γ/δ T cells in which the the expression of endogenous TCRγ and/or TCR chains have been down-regulated or eliminated are represented by SEQ ID NO: 3912 and 3913. 
     The disclosure also provides that the expression and activity of CD3ε/γ/δ TFP can be restored in T cells with impaired or lack of expression the native TCRα/β/γ or δ chains by re-expressing fragments or variants of the constant chains of TCRα/β/γ or δ. The of fragments/variants of constant chains of TCRα/β/γ and δ that can be used to restore the expression of CD3ε/γ/δ TFP in cells lacking the native TCRα/β/γ or δ chains are provided in SEQ ID Nos: 15141-15144 (Table 6D). The expression cassettes encoding these chains with a IgH signal peptide are listed in SEQ ID Nos: 15145-15148 (Table 7). 
     The disclosure further provides that the expression and activity of CD3ε/γ/δ TFP can be restored in T cells with impaired or lack of expression native TCRα/β/γ or δ chains by coexpression of a SIR or an Ab-TCR comprising the missing TCRα/β/γ or δ constant chains. Thus, in a αβ T cells with impaired or lack of expression of the native TCRa chain, the expression and activity of a CD3ε/γ/δ TFP can be rescued by expression of a SIR comprising a TCRα constant chain. In an exemplary embodiment, in a αβ T cells with impaired or lack of expression of the native TCRα chain, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a SIR (e.g., a SIR represented by SEQ ID NO: 9668, 9669, or 9684 etc.) comprising a TCRα constant chain. In another exemplary embodiment, in a αβ T cells with impaired or lack of expression of the native TCRα chain, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a Ab-TCR (e.g., a Ab-TCR represented by SEQ ID NO: 9677 or 9678 etc.) comprising a portion of TCRα constant chain. The disclosure provides that for combination therapies with allogeneic T cells involving two CARs, a CD3a/γ/δ TFP is preferably combined with a SIR and/or a Ab-TCR which incorporate the TCR constant chain or TCR constant chain fragment whose expression is reduced or missing in the allogeneic T cells. 
     The disclosure further provides that in a αβ T cells with impaired or lack of expression of the native TCRβ chains, the expression and activity of a CD3ε/γ/δ TFP can be rescued by expression of a SIR comprising a TCRβ constant chain. In an exemplary embodiment, in a αβ T cells with impaired or lack of expression of the native TCRβ1/02 chains, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a SIR (e.g., a SIR represented by SEQ ID NO: 9668, 9669, or 9684 etc.) comprising a TCRβ constant chain. In another exemplary embodiment, in a αβ T cells with impaired or lack of expression of the native TCRα chain, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a Ab-TCR (e.g., a Ab-TCR represented by SEQ ID NO: 9677 or 9678 etc.) comprising a portion of TCRβ constant chain. 
     The disclosure further provides that in a γδ T cells with impaired or lack of expression of the native TCRγ chain, the expression and activity of a CD3ε/γ/δ TFP can be rescued by expression of a SIR comprising a TCRγ constant chain. In an exemplary embodiment, in a γδ T cells with impaired or lack of expression of the native TCRγ chain, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a SIR (e.g., a SIR represented by SEQ ID NO: 9689) comprising a TCRγ constant chain. In another exemplary embodiment, in a γδ T cells with impaired or lack of expression of the native TCRγ chain, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a Ab-TCR (e.g., a Ab-TCR represented by SEQ ID NO: 9676) comprising a portion of TCRγ constant chain. 
     The disclosure further provides that in a γδ T cells with impaired or lack of expression of the native TCR6 chain, the expression and activity of a CD3ε/γ/δ TFP can be rescued by expression of a SIR comprising a TCR6 constant chain. In an exemplary embodiment, in a γδ T cells with impaired or lack of expression of the native TCR6 chain, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a SIR (e.g., a SIR represented by SEQ ID NO: 9689) comprising a TCR6 constant chain. In another exemplary embodiment, in a γδ T cells with impaired or lack of expression of the native TCR6 chain, the expression and activity of a CD3ε/γ/δ TFP (e.g., a TFP encoded by SEQ ID NOs: 8708-8714) can be rescued by expression of a Ab-TCR (e.g., a Ab-TCR represented by SEQ ID NO: 9676) comprising a portion of TCR6 constant chain. 
     The disclosure also provides methods and constructs that allow a next generation CAR (e.g., SIR and AbTCR), cTCR, and TCR to be expressed under the physiological regulatory mechanisms afforded by endogenous TCR genes. The disclosure also provides methods and constructs that allow a next generation CAR (e.g., SIR and AbTCR), cTCR, and TCR to be expressed under the promoter and 3′ untranslated regulatory mechanisms afforded by endogenous TCR genes. In one embodiment, the disclosure provides methods so that an expression cassette encoding a SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRα, TCRβ1/02, TCRγ or TCR6 gene locus. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRα gene locus (TRAC) so that the TCRα constant chain of the SIR/cTCR/Ab-TCR/TCR is expressed wholly or in part from the endogenous native TCRα constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRα gene locus (TRAC) so that the TCRα constant chain of the SIR/cTCR/Ab-TCR/TCR is encoded completely or in part by at least one of the exons of the endogenous TCRα constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRα gene locus (TRAC) so that the TCRα constant chain of the SIR/cTCR/Ab-TCR/TCR shares completely or in part the 3′ untranslated region and polyadenylation sequence of the native/endogenous TCRα constant chain gene. 
     In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRβ gene locus (TRBC) so that the TCRβ constant chain of the SIR/cTCR/Ab-TCR/TCR is expressed wholly or in part from the endogenous native TCRβ1 or TCRβ2 constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRβ1/02 gene locus (TRBC) so that the TCRβ constant chain of the SIR/cTCR/Ab-TCR/TCR is encoded completely or in part by at least one of the exons of the endogenous TCRβ constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRβ1/02 gene locus (TRBC) so that the TCRβ constant chain of the SIR/cTCR/Ab-TCR/TCR shares completely or in part the 3′ untranslated region and polyadenylation sequence of the native/endogenous TCRβ constant chain gene. 
     In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRγ gene locus (TRGC) so that the TCRγ constant chain of the SIR/cTCR/Ab-TCR/TCR is expressed wholly or in part from the endogenous native TCRγ constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRγ gene locus (TRGC) so that the TCRγ constant chain of the SIR/cTCR/Ab-TCR/TCR is encoded completely or in part by at least one of the exons of the endogenous TCRγ constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCRγ gene locus (TRGC) so that the TCRγ constant chain of the SIR/cTCR/Ab-TCR/TCR shares completely or in part the 3′ untranslated region and polyadenylation sequence of the native/endogenous TCRγ constant chain gene. 
     In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCR gene locus (TRDC) so that the TCR constant chain of the SIR/cTCR/Ab-TCR/TCR is expressed wholly or in part from the endogenous native TCR constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCR gene locus (TRGC) so that the TCR constant chain of the SIR/cTCR/Ab-TCR/TCR is encoded completely or in part by at least one of the exons of the endogenous TCR constant chain gene. In an embodiment, the SIR/cTCR/Ab-TCR/TCR is targeted to the endogenous TCR gene locus (TRDC) so that the TCR constant chain of the SIR/cTCR/Ab-TCR/TCR shares completely or in part the 3′ untranslated region and polyadenylation sequence of the native/endogenous TCR constant chain gene. 
     T cells or natural killer (NK) or stem cells, can be obtained from a subject. The term “subject” is intended to include living organisms in which an immune response can be elicited (e.g., mammals). Examples of subjects include humans, monkeys, chimpanzees, dogs, cats, mice, rats, and transgenic species thereof. T cells can be obtained from a number of sources, including peripheral blood mononuclear cells, bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, and tumors. T cells could be tissue resident gamma-delta T cells, which can be cultured and expanded in vitro prior to expression of the CAR/TCR and/or an NF-κB stimulatory molecule. 
     In certain embodiments of the disclosure, immune effector cells, e.g., T cells, can be obtained from a unit of blood collected from a subject using any number of techniques known to the skilled artisan, such as FicollTM separation. In one preferred aspect, cells from the circulating blood of an individual are obtained by apheresis. The apheresis product usually contains lymphocytes, including T cells, monocytes, granulocytes, B cells, other nucleated white blood cells, red blood cells, and platelets. In one aspect, the cells collected by apheresis may be washed to remove the plasma fraction and, optionally, to place the cells in an appropriate buffer or media for subsequent processing steps. In one embodiment, the cells are washed with phosphate buffered saline (PBS). In an alternative embodiment, the wash solution lacks calcium and may lack magnesium or may lack many if not all divalent cations. 
     Initial activation steps in the absence of calcium can lead to magnified activation. As those of ordinary skill in the art would readily appreciate a washing step may be accomplished by methods known to those in the art, such as by using a semi -automated “flow-through” centrifuge (for example, the Cobe 2991 cell processor, the Baxter CytoMate, or the Haemonetics Cell Saver 5) according to the manufacturer&#39;s instructions. After washing, the cells may be resuspended in a variety of biocompatible buffers, such as, for example, Ca-free, Mg-free PBS, PlasmaLyte A, or other saline solution with or without buffer. Alternatively, the undesirable components of the apheresis sample may be removed and the cells directly resuspended in culture media. 
     It is recognized that the methods of the application can utilize culture media conditions comprising 5% or less, for example 2%, human AB serum, and employ known culture media conditions and compositions, for example those described in Smith et al., “Ex vivo expansion of human T cells for adoptive immunotherapy using the novel Xeno-free CTS Immune Cell Serum Replacement” Clinical &amp; Translational Immunology (2015) 4, e31; doi: 10.1038/cti.2014.31. 
     In one aspect, T cells are isolated from peripheral blood lymphocytes by lysing the red blood cells and depleting the monocytes, for example, by by counterflow centrifugal elutriation or centrifugation through a PERCOLLTM gradient. 
     In one embodiment, the disclosure provides methods of treating or preventing a disease by providing to the subject in need thereof immune effector cells (e.g., T cells) or stem cells that can give rise to immune effector cells that are engineered to express an X-CAR or a X-TCR and an NF-κB stimulatory molecule, wherein X represents a disease associated antigen as described herein, and wherein the disease causing or disease-associated cells express said X antigen. Table 9 provides a list of different antigens and the exemplary diseases that can be prevented, inhibited or treated using immune effector cells expressing CARs targeting these antigens. 
     In another embodiment, the disclosure provides methods of treating or preventing a cancer, infection, autoimmune or allergic diseases by providing to the subject in need thereof immune effector cells (e.g., T cells) or stem cells that can give rise to immune effector cells that are engineered to express a non-naturally occurring immune receptor (e.g., CAR and/or TCR) of the disclosure and/or an NF-κB stimulatory molecule. In one embodiment, the NF-κB stimulatory molecule is a selective NF-κB activator. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is a non-viral NF-κB activator. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is not a transmembrane protein and is expressed in the cytosol or is preferentially present in the cytosol. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is constitutively active. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is not constitutively active. In one embodiment, the selective NF-κB activator is activated by the administration of an inducer (e.g., a dimerizer). In one embodiment, the selective NF-κB activator is vFLIP K13, NEMO-K277A or its derivatives. The CAR/NF-κB stimulatory molecule-expressing immune effector cells are administered to the patient. In one aspect the disease associated cell is a cancer cell, an infected cell (e.g., HIV-1 infected cell), or a plasma cell or a B cell or a T cell. 
     In another embodiment, the disclosure provides methods of treating or preventing a cancer, infection, autoimmune or allergic diseases by providing to the subject in need thereof immune effector cells (e.g., T cells) or stem cells that can give rise to immune effector cells that are engineered to express a naturally occurring immune receptor (e.g., a native TCR) and an NF-κB stimulatory molecule. In one embodiment, the NF-κB stimulatory molecule is a selective NF-κB activator. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is a non-viral NF-κB activator. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is not a transmembrane protein and is expressed in the cytosol or is preferentially present in the cytosol. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is constitutively active. In one embodiment, the NF-κB activator, e.g., a selective NF-κB activator, is not constitutively active. In one embodiment, the selective NF-κB activator is activated by the administration of an inducer (e.g., a dimerizer). In one embodiment, the selective NF-κB activator is vFLIP K13, NEMO-K277A or its derivatives. The native TCR and NF-κB stimulatory molecule-expressing immune effector cells are administered to the patient. In one aspect the disease associated cell is a cancer cell, an infected cell (e.g., HIV-1 infected cell), or a plasma cell or a B cell or a T cell. 
     In another embodiment, the disclosure provides methods of treating or preventing a cancer, infection, autoimmune or allergic diseases by providing to the subject in need thereof immune effector cells (e.g., T cells) or stem cells that can give rise to immune effector cells that are engineered to express a naturally occurring (e.g., native TCR) or a non-naturally occurring immune receptor (e.g., CAR and/or recombinant TCR) of the disclosure and/or an NF-κB stimulatory molecule. in some embodiments, the activity of CAR-T or TCR-T cells may be controlled using a water soluble salt of Dasatinib. 
     In another aspect, a method of treating a subject, e.g., reducing or ameliorating a hyperproliferative disorder or condition (e.g., a cancer), e.g., solid tumor, a soft tissue tumor, a blood cancer, or a metastatic lesion, in a subject is provided. 
     In yet another embodiment, the disclosure pertains to a method of treating a diasease in a subject. The method comprises administering to the subject a cell expressing a naturally occurring and/or a non-naturally occurring immune receptor (e.g., CAR and/or recombinant TCR) of the disclosure and/or an NF-κB stimulatory molecule of the disclosure such that the disease is treated in the subject. In one aspect the method comprises administering to the subject a cell expressing its endogenous (or native) TCR and an NF-κB stimulatory molecule of the disclosure such that the disease is treated in the subject. In one aspect, the disease associated with expression of a disease associate antigen as described herein is an infectious disease. In one aspect the infectious disease is disease associated with infection by HIV1, HIV2, HTLV1, Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus, adeno-associated virus, BK virus, Human Herpesvirus 6, Human Herpesvirus 8, influenza A virus, influenza B virus parainfluenza virus, avian flu virus, MERS and SARS coronaviruses, Crimean Congo Hemorrhagic fever virus, rhino virus, enterovirus, Dengue virus, West Nile virus, Ebola virus, Marburg virus, Lassa fever virus, zika virus, RSV, measles virus, mumps virus, rhino virus, varicella virus, herpes simplex virus 1 and 2, varicella zoster virus, HIV-1, HTLV1, Hepatitis virus, enterovirus, hepatitis B virus, Hepatitis C virus, Nipah and Rift valley fever viruses, Japanese encephalitis virus, mycobacterium tuberculosis, atypical mycobacteria species, Pneumocystis jirovecii, toxoplasmosis, rickettsia, nocardia, aspergillus, mucor, or candida. 
     In some embodiments, the non-naturally occurring immune receptor (e.g., CAR and/or TCR) specifically binds an HIV antigen. In some embodiments, the HIV antigen is an HIV-1 antigen. In some embodiments, the HIV antigen is an HIV envelope protein or a portion thereof. In some embodiments, the HIV antigen is gp120 or a portion thereof. In some embodiments the HIV antigen is the CD4 binding site on gp120. In some embodiments, the HIV antigen is the CD4-induced binding site on gp120. In some embodiments, the HIV antigen is the N-glycan on gp120. In some embodiments, the HIV antigen is the V2 of gp120. In some embodiments, the HIV antigen is the membrane proximal region on gp41. 
     The disclosure includes a type of cellular therapy where immune effector cells (e.g., T cells or stem cells that give rise to T cells) are genetically modified to express a CAR or TCR of the disclosure and/or an NF-κB stimulatory molecule and the CAR-expressing T cell or stem cell is infused to a recipient in need thereof. The disclosure also includes a type of cellular therapy where immune effector cells (e.g., T cells or stem cells that give rise to T cells) are genetically modified to express a NF-κB stimulatory molecule and such cells are infused to a recipient in need thereof. The infused cells are able to kill disease associated cells (e.g., tumor cells or virally infected cells) in the recipient. Unlike antibody therapies, the NF-κB activator modified immune effector cells (e.g., T cells, stem cells) are able to replicate in vivo resulting in long-term persistence that can lead to sustained tumor control. In various aspects, the NF-κB activator modified immune effector cells (e.g., T cells or stem cells that can give rise to T cells) administered to the patient, or their progeny, persist in the patient for at least four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, thirteen months, fourteen month, fifteen months, sixteen months, seventeen months, eighteen months, nineteen months, twenty months, twenty-one months, twenty-two months, twentythree months, two years, three years, four years, or five years after administration of the T cell or stem cells to the patient. 
     The disclosure also includes a type of cellular therapy where stem cells (e.g., hematopoietic stem cell or lymphoid stem cells or embryonic stem cells, or induced pluripotent stem cells) that are capable of giving rise to immune effector cells (e.g., T cells) are modified to express a non-naturally occurring immune receptor (e.g., CAR and/or TCR) of the disclosure and/or an NF-κB stimulatory molecule and are administered to a recipient in need thereof. The administered stem cells give rise to immune effector cells (e.g., T cells) after transplantation into the recipient, which (i.e. the immune effector cells) are able to kill disease associated cells in the recipient. Thus, in various aspects, the immune effector cells (e.g., T cells) that are produced in the patient after administration of CAR/NFκB-activator-expressing stem cells, persist in the patient for at least one week, 2 weeks, 3 weeks, one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, thirteen months, fourteen month, fifteen months, sixteen months, seventeen months, eighteen months, nineteen months, twenty months, twenty-one months, twenty-two months, twenty-three months, two years, three years, four years, five years, ten years or twenty years after administration of the T cell or stem cells to the patient. The disclosure also includes a type of cellular therapy where stem cells that are capable of giving rise to immune effector cells (e.g., T cells) are modified to express a non-naturally occurring immune receptor (e.g., CAR and/or TCR) of the disclosure and/or an NF-κB stimulatory molecule and are differentiated in vitro to generate immune effector cells that are infused to a recipient in need thereof. The infused immune effector cells (e.g., T cells) after infusion into the recipient are able to kill disease associated cells in the recipient. Thus, in various aspects, the immune effector cells (e.g., T cells) that are administered to the patient persist in the patient for at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, one week, 2 weeks, 3 weeks, one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, thirteen months, fourteen month, fifteen months, sixteen months, seventeen months, eighteen months, nineteen months, twenty months, twenty-one months, twenty-two months, twentythree months, two years, three years, four years, five years, ten years or twenty years. 
     The disclosure includes a type of cellular therapy where immune effector cells (e.g., T cells or stem cells that give rise to T cells) are genetically modified to express CARs targeting two or more different antigens in the same cell and such T cell or stem cell is infused to a recipient in need thereof. In an embodiment, at least one of the CARs targets an antigen expressed on the hematopoietic cells. In an embodiment, at least one of the CARs targets an antigen selected from the group of CD19, CD20, CD22, BCMA, CS1, CD138, Lyml, Lym2, CD33 and CD123. In an embodiment, at least one of the CARs targets an antigen expressed on the hematopoietic cells and at least one other CARs targets and antigen expressed on solid tumors. In an embodiment, at least one of the CARs targets an antigen selected from the group of CD19, CD20, CD22, BCMA, CS1, CD138, Lyml, Lym2, CD33 or CD123 and at least one other CAR targets an antigen selected from the group of Mesothelin, Her2, Folate Receptor 1, ROR1, IL13Ra2, AFP, WT1, Ras, NY-ESO-1, DLL3, CD70 and PTK7. In an embodiment, at least one of the CARs is a SIR. In an embodiment, at least one of the CARs is an Ab-TCR. In an embodiment, at least one of the CARs is a SIR and the other CAR is a CD3ε/γ/δ TFP. In an embodiment, at least one of the CARs is a Ab-TCR and the other CAR is a CD3ε/γ/δ TFP. In an embodiment, the cells have impaired expression of at least one of the native TCR chains. The disclosure also includes a type of cellular therapy where immune effector cells (e.g., T cells or stem cells that give rise to T cells) are genetically modified to express CARs targeting two different antigens and an NF-κB stimulatory molecule and such cells are infused to a recipient in need thereof. In embodiment, the cells are autologous while in other embodiments the cells are allogenic. The infused cells are able to kill disease associated cells (e.g., tumor cells or virally infected cells) in the recipient. 
     With respect to ex vivo immunization, at least one of the following occurs in vitro prior to administering the cell into a mammal: i) expansion of the cells, ii) introducing a nucleic acid encoding a non-naturally occurring immune receptor (e.g., CAR and/or TCR) of the disclosure and/or an NF-κB stimulatory molecule to the cells or iii) cryopreservation of the cells. 
     Ex vivo procedures are well known in the art and are discussed more fully below. Briefly, cells are isolated from a mammal (e.g., a human) and genetically modified (i.e., transduced or transfected in vitro) with a one or more vectors that express a non-naturally occurring immune receptor (e.g., CAR and/or TCR) of the disclosure and/or an NF-κB stimulatory molecule disclosed herein. The non-naturally occurring immune receptor (e.g., CAR and/or TCR) and NF-κB activator-modified cell can be administered to a mammalian recipient to provide a therapeutic benefit. The mammalian recipient may be a human and the non-naturally occurring immune receptor (e.g., CAR and/or TCR) and NF-κB activator-modified cell can be autologous with respect to the recipient. Alternatively, the cells can be allogeneic, syngeneic or xenogeneic with respect to the recipient. 
     The procedure for ex vivo expansion of hematopoietic stem and progenitor cells is described in U.S. Pat. No. 5,199,942, incorporated herein by reference, can be applied to the cells of the present invention. Other suitable methods are known in the art, therefore the present invention is not limited to any particular method of ex vivo expansion of the cells. Briefly, ex vivo culture and expansion of immune effector cells (e.g., T cells) comprises: (1) collecting CD34+ hematopoietic stem and progenitor cells from a mammal from peripheral blood harvest or bone marrow explants; and (2) expanding such cells ex vivo. In addition to the cellular growth factors described in U.S. Pat. No. 5,199,942, other factors such as flt3-L, IL-1, IL-3 and c-kit ligand, can be used for culturing and expansion of the cells. 
     Generally, the cells activated and expanded as described herein may be utilized in the treatment and prevention of diseases that arise in individuals who are immunocompromised. In certain aspects, the cells of the disclosure are used in the treatment of patients at risk for developing diseases, disorders and conditions associated with expression of a disease associate antigen as described herein. Thus, the disclosure provides methods for the treatment or prevention of diseases, disorders and conditions associated with expression of a disease associate antigen as described herein comprising administering to a subject in need thereof, a therapeutically effective amount of the CAR/TCR/NF-κB stimulatory molecule-modified immune effector cells (e.g., T cells) or stem cells that are capable of generating immune effector cells of the disclosure. 
     In one aspect the CAR/TCR/NF-κB stimulatory molecule-expressing cells of the disclosures may be used to treat a proliferative disease such as a cancer or malignancy or is a precancerous condition such as a myelodysplasia, a myelodysplastic syndrome or a preleukemia. Further a disease associated with a cancer associate antigen as described herein expression include, but not limited to, e.g., atypical and/or non-classical cancers, malignancies, precancerous conditions or proliferative diseases expressing a cancer associated antigen as described herein. Noncancer related indications associated with expression of a disease associate antigen as described herein include, but are not limited to, e.g., autoimmune disease, (e.g., lupus), inflammatory disorders (allergy and asthma), infectious conditions (e.g., HIV1, CMV, EBV, influenza) and transplantation. 
     The CAR/TCR/NF-κB stimulatory molecule-modified immune effector cells (e.g., T cells) of the disclosure may be administered either alone, or as a pharmaceutical composition in combination with diluents and/or with other components such as IL-2 or other cytokines or cell populations. 
     Hematological cancer or blood cancer conditions are the types of cancer such as leukemia, lymphoma, and malignant lymphoproliferative conditions that affect blood, bone marrow and the lymphatic system. 
     Leukemia can be classified as acute leukemia and chronic leukemia. Acute leukemia can be further classified as acute myelogenous leukemia (AML) and acute lymphoid leukemia (ALL). Chronic leukemia includes chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Other related conditions include myelodysplastic syndromes (MDS, formerly known as “preleukemia”) which are a diverse collection of hematological conditions united by ineffective production (or dysplasia) of myeloid blood cells and risk of transformation to AML. 
     Lymphoma is a group of blood cell tumors that develop from lymphocytes. Exemplary lymphomas include non-Hodgkin lymphoma and Hodgkin lymphoma. 
     The disclosure provides for compositions and methods for treating and preventing cancer. In one aspect, the cancer is a hematologic cancer or blood cancer including but is not limited to hematological cancer is a leukemia or a lymphoma. In one aspect, the CAR/TCR/NFKB-expressing cells of the disclosure may be used to treat cancers and malignancies such as, but not limited to, e.g., acute leukemias including but not limited to, e.g., B-cell acute lymphoid leukemia (“BALL”), T-cell acute lymphoid leukemia (“TALL”), acute lymphoid leukemia (ALL); one or more chronic leukemias including but not limited to, e.g., chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL); additional hematologic cancers or hematologic conditions including, but not limited to, e.g., B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt&#39;s lymphoma, diffuse large B cell lymphoma, Follicular lymphoma, Hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, Marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and “preleukemia” which are a diverse collection of hematological conditions united by ineffective production (or dysplasia) of myeloid blood cells, and the like. Further a disease associated with a cancer associate antigen as described herein expression includes, but not limited to, e.g., atypical and/or non-classical cancers, malignancies, precancerous conditions or proliferative diseases expressing a cancer associate antigen as described herein. 
     The disclosure provides a method of administering to a subject an effective amount of a cell, e.g., an immune effector cell, or a population thereof, each cell comprising a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule, optionally in combination with an agent that increases the efficacy and/or safety of the immune cell. In various embodiments, the agent that increases the efficacy and/or safety of the immune cell is selected from the group consisting of (i) a protein phosphatase inhibitor; (ii) a kinase inhibitor; (iii) a cytokine; (iv) an inhibitor of an immune inhibitory molecule; (v) an agent that decreases the level or activity of a TREG cell; (vi) an agent that increase the proliferation and/or persistence of a CAR/NF-κB stimulatory molecule-modified cells; (vii) a chemokine; (viii) an agent that increases the expression of CARs/TCRs; (ix) an agent that allows regulation of the expression or activity of a CAR; (x) an agent that allows control over the survival and/or persistence of the modified cells; (xi) an agent that controls the side effects of the modified cells; (xii) a Brd4 inhibitor; (xiii) an agent that delivers a therapeutic (e.g. sHVEM) or prophylactic agent to the site of the disease; (xiv) an agent that increases the expression of the target antigen against which the CAR is directed; (xv) an adenosine A2a receptor antagonist; and (xvi) any combination of (i)-(xv). 
     In some embodiments, the disease to be treated or prevented is a hematologic cancer. In further embodiments, the hematologic cancer is leukemia. Non-limiting examples of acute leukemias include B-cell acute lymphoid leukemia (“BALL”), T -cell acute lymphoid leukemia (“TALL”), acute lymphoid leukemia (ALL); one or more chronic leukemias including but not limited to chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL); additional hematologic cancers or hematologic conditions including, but not limited to B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt&#39;s lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, Marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, nonHodgkin lymphoma, Hodgkin lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and “preleukemia” which are a diverse collection of hematological conditions united by ineffective production (or dysplasia) of myeloid blood cells, and to disease associated with expression of a tumor antigen described herein include, but not limited to, atypical and/or non-classical cancers, malignancies, precancerous conditions or proliferative diseases expressing a tumor antigen as described herein; and any combination thereof. In another embodiment, the disease associated with a tumor antigen described herein is a solid tumor. 
     In some embodiments, the tumor antigen associated with the disease is selected from: CD5, CD19; CD123; CD22; CD30; CD171; CS-1 (also referred to as CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1 or CLECL1); CD33; epidermal growth factor receptor variant III (EGFRviii); ganglioside G2 (GD2); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TNF receptor family member B cell maturation (BCMass.); Tn antigen ((Tn Ag) or (GalNAca-Ser/Thr)); prostate-specific membrane antigen (PSMass.); Receptor tyrosine kinase-like orphan receptor 1 (ROR1); FmsLike Tyrosine Kinase 3 (FLT3); Tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; a glycosylated CD43 epitope expressed on acute leukemia or lymphoma but not on hematopoietic progenitors, a glycosylated CD43 epitope expressed on non-hematopoietic cancers, Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2); Mesothelin; Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 21 (Testisin or PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet-derived growth factor receptor beta (PDGFR-beta); Stage-specific embryonic antigen-4 (SSEA-4); CD20; Folate receptor alpha; Receptor tyrosine-protein kinase ERBB2 (Her2/neu); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); neural cell adhesion molecule (NCAM); Prostase; prostatic acid phosphatase (PAP); elongation factor 2 mutated (ELF2M); Ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CA1X); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); glycoprotein 100 (gp100); oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl); tyrosinase; ephrin type-A receptor 2 (EphA2); Fucosyl GM1; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDClalp(1-4)bDG1cp(1-1)Cer); transglutaminase 5 (TGSS); high molecular weight-melanomaassociated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Polysialic acid; placenta-specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); Cancer/testis antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-1a); Melanoma-associated antigen 1 (MAGE-A1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member lA (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; prostein; surviving; telomerase; prostate carcinoma tumor antigen-1 (PCT A-1 or Galectin 8), melanoma antigen recognized by T cells 1 (MelanA or MARTI); Rat sarcoma (Ras) mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); N-Acetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin Bl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Tyrosinase-related protein 2 (TRP-2); Cytochrome P4501B 1 (CYP1B 1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or Brother of the Regulator oflmprinted Sites), Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3); Paired box protein Pax-5 (PAXS); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint 2 (SSX2); Receptor for Advanced Glycation End products (RAGE-1); renal ubiquitous 1 (RU1); renal ubiquitous 2 (RU2); legumain; human papilloma virus E6 (HPV E6); human papilloma virus E7 (HPV E7); intestinal carboxyl esterase; heat shock protein 70-2 mutated (mut hsp70-2); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIRD; Fc fragment of IgA receptor (FCAR or CD89); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRLS); and immunoglobulin lambda-like polypeptide 1 (IGLLl), MPL, Biotin, c-MYC epitope Tag, CD34, LAMP1 TROP2, GFRalpha4, CDH17, CDH6, NYBR1, CDH19, CD200R, Slea (CA19.9; Sialyl Lewis Antigen) Fucosyl-GM1, PTK7, gpNMB, CDH1-CD324, DLL3, CD276/B7H3, IL11Rα, IL13Ra2, CD179b-IGL11, ALK TCRgamma-delta, NKG2D, CD32 (FCGR2A), CSPG4-HMW-MAA, Tim1-/HVCR1, CSF2RA (GM-CSFR-alpha), TGFbetaR2, VEGFR2/KDR, Lews Ag, TCR-betal chain, TCR-beta2 chain, TCR-gamma chain, TCR-delta chain, FITC, Leutenizing hormone receptor (LHR), Follicle stimulating hormone receptor (FSHR), Chorionic Gonadotropin Hormone receptor (CGHR), CCR4, SLAMF6, SLAMF4, HIV1 envelope glycoprotein, HTLV1-Tax, CMV pp65, EBV-EBNA3c, influenza A hemagglutinin (HA), GAD, PDL1, Guanylyl cyclase C (GCC), KSHV-K8.1 protein, KSHV-gH protein, auto-antibody to desmoglein 3 (Dsg3), autoantibody to desmoglein 1 (Dsgl), HLA, HLA-A, HLA-A2, HLA-B, HLA-C, HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, HLA-DR, HLA-G, IGE, CD99, RAS G12V, Tissue Factor 1 (TF1), AFP, GPRC5D, claudin18.2 (CLD18A2 OR CLDN18A.2)), P-glycoprotein, STEAP1, LIV1, NECTIN-4, CRIPTO, GPA33, BST1/CD157, low conductance chloride channel, and antigen recognized by TNT antibody. 
     In some embodiments, the disease to be treated is an infectious disease including, but not limited to, infection by HIV1, HIV2, HTLV1, Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus, adeno-associated virus, BK virus, Human Herpesvirus 6, Human Herpesvirus 8 influenza virus, parainfluenza virus, avian flu virus, MERS and SARS coronaviruses, Crimean Congo Hemorrhagic fever virus, rhino virus, enterovirus, Dengue virus, West Nile virus, Ebola virus, Marburg virus, Lassa fever virus, zika virus, RSV, measles virus, mumps virus, rhino virus, varicella virus, herpes simplex virus 1 and 2, varicella zoster virus, HIV-1, HTLV1, Hepatitis virus, enterovirus, hepatitis B virus, Hepatitis C virus, Nipah and Rift valley fever viruses, Japanese encephalitis virus, mycobacterium tuberculosis, atypical mycobacteria species, Pneumocystis jirovecii, toxoplasmosis, rickettsia, nocardia, aspergillus, mucor, or candida. In such diseases, the the target antigen associated with the disease is selected from: HIV1 envelope glycoprotein, HIV1-gag, HTLV1-Tax, CMV pp65, EBV-EBNA3c, influenza A hemagglutinin (HA) and GAD. 
     The disease to be treated or prevented by the methods and compositions of the dislcosure can be an immune or degenerative disease, e.g., diabetes mellitus, multiple sclerosis, rheumatoid arthritis, pemphigus vulgaris, ankylosing spondylitis, Hoshimoto&#39;s thyroiditis, SLE, sarcoidosis, scleroderma, mixed connective tissue disease, graft versus host disease or Alzheimer&#39;s disease. In such embodiments, the target antigen associated with the disease is an autoantibody. 
     Further non-limiting examples of diseases associated with expression of a target antigen include any one of the following cancers or related conditions: colon cancer, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine, cancer of the esophagus, melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin&#39;s Disease, non-Hodgkin&#39;s lymphoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, solid tumors of childhood, cancer of the bladder, cancer of the kidney or ureter, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi&#39;s sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers, combinations of said cancers, and metastatic lesions of said cancers. 
     In certain embodiments of the methods or uses described herein, the CAR/TCR-expressing cell comprising a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule molecule is administered in combination with an agent that increases the efficacy of the immune effector cell, e.g., one or more of a protein phosphatase inhibitor, a kinase inhibitor, a cytokine, a chemokine, a scFV fragment, a bispecific antibody, an inhibitor of an immune inhibitory molecule; a cellular signaling protein, a viral signaling protein, or an agent that decreases the level or activity of a TREG cell. Non-limiting examples of protein phosphatase inhibitors include a SHP-1 inhibitor and/or an SHP-2 inhibitor. Non-limiting examples of kinase inhibitors include a CDK4 inhibitor, a CDK4/6 inhibitor (e.g., palbociclib), a BTK inhibitor (e.g., ibrutinib or RN-486), an mTOR inhibitor (e.g., rapamycin or everolimus (RAD001)), an MNK inhibitor, or a dual P13K/mTOR inhibitor. In one embodiment, the BTK inhibitor does not reduce or inhibit the kinase activity of interleukin-2-inducible kinase (ITK). Non limiting examples of an A2a receptor antagonist include Vipadenant. In some embodiments, the agent that inhibits the immune inhibitory molecule may be one or more of an antibody or antibody fragment, an inhibitory nucleic acid, a clustered regularly interspaced short palindromic repeats (CRISPR), a transcription-activator like effector nuclease (TALEN), or a zinc finger endonuclease (ZFN) that inhibits the expression of the inhibitory molecule. In other embodiments of the methods or uses described herein, the agent that decreases the level or activity of the TREG cells is chosen from cyclophosphamide, antiGITR antibody, CD25-depletion, or a combination thereof. In certain embodiments of the methods or uses described herein, the immune inhibitory molecule is selected from the group consisting of PD1, PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, TGFR beta, CEACAM-1, CEACAM-3, and CEACAM-5. In other embodiments, the cytokine is chosen from IL2, IL-7, IL-15 or IL-21, or any combination thereof. In other embodiments, the immune effector cell comprising the CAR/TCR and/or NF-κB stimulating molecule and a second, e.g., any of the combination therapies disclosed herein (e.g., the agent that that increases the efficacy of the immune effector cell) are administered substantially simultaneously or sequentially. In one embodiment the cytokine is administered to the subject simultaneously (e.g., administered on the same day) with or shortly after administration (e.g., administered 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days after administration) of the cell or population of cells comprising a CAR/TCR and/or NF-κB stimulatory molecule. In other embodiments, the cytokine is administered to the subject after a prolonged period of time (e.g., at least 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, or more) after administration of the cell or population of cells, or after assessment of the subject&#39;s response to the cell. 
     In other embodiments, the cells expressing a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule are administered in combination with an agent that ameliorates one or more side effects associated with administration of a cell expressing a CAR/TCR and/or NF-κB stimulatory molecule. Side effects associated with the CAR/TCR and/or NF-κB stimulatory molecule)-expressing cell can be chosen from cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis (HLH) or neurological complications. Examples of such agents include steroids (e.g. prednisone, dexamethasone), IL6R antagonists (e.g., tocilizumab), IL1R antagonists (e.g., anakinra), src kinase inhibitors (e.g., dasatinib or a water soluble salt of dasatinib), a kinase inhibitor (e.g., Ibrutinib), calcineurin inhibitors (e.g., tacrolimus or cyclosporine A) or chemotherapy drugs (e.g., cyclophosphamide, methotrexate or vincristine). 
     In one embodiment, the cells expressing a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule are administered in combination with a low, immune enhancing dose of an mTOR inhibitor. While not wishing to be bound by theory, it is believed that treatment with a low, immune enhancing, dose (e.g., a dose does not completely suppress the immune system but is sufficient to improve immune function) is accompanied by a reduction in PD-1 positive T cells or an increase in PD-1 negative cells. PD-1 positive T cells, but not PD-1 negative T cells, can be exhausted by engagement with cells which express a PD-1 ligand, e.g., PD-L1 or PD-L2. 
     Pharmaceutical compositions of the disclosure may comprise a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule expressing cell, e.g., a plurality of CAR/TCR and/or NF-κB stimulatory molecule-expressing cells, as described herein, in combination with one or more pharmaceutically or physiologically acceptable carriers, diluents or excipients. Such compositions may comprise buffers such as neutral buffered saline, phosphate buffered saline and the like; carbohydrates such as glucose, mannose, sucrose or dextrans, mannitol; proteins; polypeptides or amino acids such as glycine; antioxidants; chelating agents such as EDTA or glutathione; adjuvants (e.g., aluminum hydroxide); and preservatives. Compositions of the disclosure can be formulated for intravenous administration. The composition may futher comprise a secondary active agent (e.g., an anticancer, antiviral or antibiotic agent). 
     Pharmaceutical compositions of the disclosure may be administered in a manner appropriate to the disease to be treated (or prevented). The quantity and frequency of administration will be determined by such factors as the condition of the patient, and the type and severity of the patient&#39;s disease. When “an immunologically effective amount,” “an anti-tumor effective amount,” “a tumor-inhibiting effective amount,” or “therapeutic amount” or “anti-infective” is indicated, the amount of the compositions of the disclosure to be administered can be determined by a physician with consideration of individual differences in age, weight, tumor size, extent of infection or metastasis, and condition of the patient (subject) as the case may be. It can generally be stated that a pharmaceutical composition comprising the immune effector cells (e.g., T cells, NK cells) described herein may be administered at a dosage of 10 4  to 10 9 cells/kg body weight, in some instances 10 5  to 10 6  cells/kg body weight, including all integer values within those ranges. T cell compositions may also be administered multiple times at these dosages. The cells can be administered by using infusion techniques that are commonly known in immunotherapy (see, e.g., Rosenberg et al., New Eng. J. of Med. 319:1676, 1988). 
     In certain aspects, it may be desired to administer activated immune effector cells (e.g., T cells, NK cells) to a subject and then subsequently redraw blood (or have an apheresis performed), activate immune effector cells (e.g., T cells, NK cells) therefrom according to the disclosure, and reinfuse the patient with these activated and expanded immune effector cells (e.g., T cells, NK cells). This process can be carried out multiple times every few weeks. In certain aspects, immune effector cells (e.g., T cells, NK cells) can be activated from blood draws of from 10cc to 400cc. In certain aspects, immune effector cells (e.g., T cells, NK cells) are activated from blood draws of 20cc, 30cc, 40cc, 50cc, 60cc, 70cc, 80cc, 90cc, or 100cc. 
     In some embodiments, subjects may undergo leukapheresis, wherein leukocytes are collected, enriched, or depleted ex vivo to select and/or isolate the cells of interest, e.g., T cells. These T cell isolates may be expanded by methods known in the art and treated and/or transformed such that one or more constructs of the disclosure may be introduced, thereby creating a CAR-T or TCR-T cell of the disclosure coexpressing an accessory module encoding a NF-κB activator. Subjects in need thereof may subsequently undergo standard treatment with high dose chemotherapy followed by peripheral blood stem cell transplantation. In certain aspects, following or concurrent with the transplant, subjects receive an infusion of the expanded CAR-T cells or TCR-T cells of the disclosure that optionally coexpress an accessory module encoding a NF-κB activator. In an additional aspect, expanded cells are administered before or following surgery. 
     Kits to practice the disclosure are also provided. For example, kits for treating a cancer in a subject, or making a cell that expresses a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule disclosed herein. The kits may include at least one nucleic acid molecule or vector encoding a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule along with a method to introduce the nucleic acid into the immune effector cells. Th kit may include a virus comprising a nucleic acid encoding a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule and chemicals, such as polybrene, to enhance the virus transduction. The kit may contain components for isolation of T cells for expressing a non-naturally occurring immune receptor (e.g., CAR and/or TCR). Alternatively, the kit may contain immune effector cells (e.g., T cells or NK cells) or stem cells expressing a non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecule. More than one of the disclosed non-naturally occurring immune receptor (e.g., CAR and/or TCR) and/or NF-κB stimulatory molecules can be included in the kit. The kit can include a container and a label or package insert on or associated with the container. 
     Suitable containers include, for example, bottles, vials, syringes, etc. The containers may be formed from a variety of materials such as glass or plastic. The container typically holds a composition including one or more of the nucleic acid molecules, viruses, vectors, T cells etc. In several embodiments the container may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). A label or package insert indicates that the composition is used for treating the particular condition. The label or package insert typically will further include instructions for use of a disclosed components, for example, in a method of treating or preventing a tumor or of making a CAR-T cell. The package insert typically includes instructions customarily included in commercial packages of therapeutic products that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products. The instructional materials may be written, in an electronic form (such as a computer diskette or compact disk) or may be visual (such as video files). The kits may also include additional components to facilitate the particular application for which the kit is designed. Thus, for example, the kit may additionally contain means for measuring the expression of a CAR and/or NF-κB stimulatory molecule on or in T cells or of determining the number or percentage of T cells that express the CAR and/or NF-κB stimulatory molecule or of determining the functionality of cells. The kits may additionally include buffers and other reagents routinely used for the practice of a particular method. Such kits and appropriate contents are well known to those of skill in the art. 
     The disclosure is further described by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the disclosure should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. 
     EXAMPLES 
     Cell lines engineered to express luciferases (e.g., GLuc or NLuc) for measuring cytotoxicity of different constructs targeting different cell surface and intracellular antigens are provided in Table A. Cell lines used in this experiments, target antigens on the cells lines and their growth media are shown in the following Table A. Cells were cultured at 37° C., in a 5% CO2 humidified incubator. The cell lines were obtained from ATCC, NIH AIDS reagent program or were available in the laboratory. 
     
       
         
           
               
               
               
             
               
                 TABLE A 
               
               
                   
               
               
                   
                 Culture 
                 Exemplary CAR Target Antigens 
               
               
                 Cell line 
                 Conditions 
                 Expressed 
               
               
                   
               
             
            
               
                 BC-1 
                 RPMI, 20% FCS 
                 BCMA, GPRC, CD138 
               
               
                 BC-3 
                 RPMI, 20% FCS 
                 BCMA, GPRC, CD138 
               
               
                 BCBL-1 
                 RPMI, 20% FCS 
                 GPRC, CD138 
               
               
                 JSC-1 
                 RPMI, 20% FCS 
                 GPRC, CD138 
               
               
                 MM1S 
                 RPMI, 10% FCS 
                 CD38, GPRC, CD44, CD200R 
               
               
                 U266 
                 RPMI, 10% FCS 
                 BCMA, WT1/HLA-A2+, CS1, CLL1, CD138, 
               
               
                   
                   
                 c-MET, IL6R, CD179b, NY-ESO/HLA-A2, 
               
               
                   
                   
                 NYBR, LAMP1 
               
               
                 L363 
                 RPMI, 10% FCS 
                 BCMA, GPRC, WT1/HLA-A2+, CS1, CLL1, 
               
               
                   
                   
                 CD138, NY-ESO/HLA-A2, NYBR, LAMP1 
               
               
                 K562 
                 RPMI, 10% FCS 
                 CD33, IL1Ra, TnAg 
               
               
                 BV173 
                 RPMI, 10% FCS 
                 CD123, CD179b, IL1Ra, WT1/HLA- 
               
               
                   
                   
                 A2+, CXCR4, FLT3, CD179a 
               
               
                 Nalm6 
                 RPMI, 10% FCS 
                 CD19, CD20, CD22, CD179b, CD179a 
               
               
                 HL60 
                 RPMI, 10% FCS 
                 CD33, CD34, CLL1, IL6R, CD32, CD179 
               
               
                 U937 
                 RPMI, 10% FCS 
                 CD4, CLL1 
               
               
                 RS:411 
                 RPMI, 20% FCS 
                 CD19, Folate Receptor beta (FRbeta), 
               
               
                   
                   
                 TGFbeta, CD179b, NKG2DNKG2D, FLT3, 
               
               
                   
                   
                 CD179a 
               
               
                 MV:411 
                 RPMI, 10% FCS 
                 FLT3, CD123, FRbeta 
               
               
                 Raji 
                 RPMI, 10% FCS 
                 CD19, CD20, CD22, BCMA, CD38, CD70, 
               
               
                   
                   
                 CD79, Folate Receptor beta, CLL1 
               
               
                 HEL-92.1.7 
                 RPMI, 10% FCS 
                 MPL, CD33, CD32, CD200R 
               
               
                 (HEL) 
               
               
                 Jurkat 
                 RPMI, 10% FCS 
                 TnAg, TSLRP, TSHR, CD4, CD38 
               
               
                 Daudi 
                 RPMI, 10% FCS 
                 BCMA, FRbeta 
               
               
                 REC-1 
                 RPMI, 10% FCS 
                 NKG2DNKG2D, ROR1 
               
               
                 KG-1 
                 RPMI, 20% FCS 
                 CD33, CD34, CD123, TSLRP 
               
               
                 CEM 
                 RPMI, 10% FCS 
                 CD5, CD43 
               
               
                 U937 
                 RPMI, 10% FCS 
                 CD4, CLL1 
               
               
                 LAMA5 
                 RPMI, 10% FCS 
                 WT1/HLA-A2 
               
               
                 A549 
                 DMEM, 10% FCS 
                 ROR1, CD22, TIM1, CDH17 
               
               
                 HT29 
                 DMEM, 10% FCS 
                 EGFR, SLEA, c-MET 
               
               
                 Molm-13 
                 RPMI, 20% FCS 
                 FLT3, IL6R, LAMP1, TSLRP, CD4, 
               
               
                   
                   
                 CSF2RA, CXCR4, IL6R, CSF2RA, GPC3 
               
               
                 A431 
                 DMEM, 10% FCS 
                 EGFR, Folate Receptor Alpha, Her3 
               
               
                 P19 
                 DMEM, 10% FCS 
                 SSEA 
               
               
                 THP-1 
                 RPMI, 10% FCS 
                 CD32, CD33, CXCR4, CD123, CD44, IL6R, 
               
               
                   
                   
                 Folate Receptor beta, CD70, LAMP1, 
               
               
                   
                   
                 FLT3, CSF2RA 
               
               
                 U87MG 
                 DMEM, 10% FCS 
                 CD276, gpNMB, IL13RA2 
               
               
                 LoVo 
                 DMEM, 10% FCS 
                 Tissue Factor, CDH17, EGFR 
               
               
                 SKOV-3 
                 DMEM, 10% FCS 
                 Folate Receptor alpha (FR1), FSHR, 
               
               
                   
                   
                 Her2, Her3, LHR, MSLN, TIM1, EPCAM 
               
               
                 NCI-H1993 
                 DMEM, 10% FCS 
                 EGFR 
               
               
                 Kasumi-1 
                 RPMI, 20% FCS 
                 CLEC5A, PR1/HLA-A2, TGFbeta, 
               
               
                 Jeko-1 
                 RPMI, 20% FCS 
                 BCMA, ROR1 
               
               
                 PC-3 
                 DMEM, 10% FCS 
                 CGH, TROP2, PSCA, PSMA. EPCAM, FSHR, 
               
               
                   
                   
                 CLD18A2 (CLDN18.2) 
               
               
                 HeLa 
                 DMEM, 10% FCS 
                 EGFR, FR1, MSLN, TSHR 
               
               
                 LnCap 
                 DMEM, 10% FCS 
                 EGFR, FSHR, PSCA, PSMA, CD22, Her3, 
               
               
                   
                   
                 CD22, LHR, CLD18A2 (CLDN18.2) 
               
               
                 OVCAR-3 
                 DMEM, 10% FCS 
                 B7H4, CDH6, DLL3, FR1, FSH, LHR, MSLN, 
               
               
                   
                   
                 PTK7, TnAg, TSHR, L1CAM 
               
               
                 MEL-624 
                 DMEM, 10% FCS 
                 CDH19, GD2, GD3, gp100/HLA-A2, gpNMB, 
               
               
                   
                   
                 HMWMAA, NYESO/HLA-A2, MART1/HLA-A2 
               
               
                 LS174-T 
                 DMEM, 10% FCS 
                 CEA 
               
               
                 MEL-526 
                 DMEM, 10% FCS 
                 GD2 
               
               
                 MDA-MB231 
                 DMEM, 10% FCS 
                 CD324, Muc1 
               
               
                 L1236 
                 RPMI, 20% FCS 
                 CD30, CD23, PDL1 
               
               
                 L428 
                 RPMI, 20% FCS 
                 CD30, CD123, CCR4, PDL1 
               
               
                 L540 
                 RPMI, 20% FCS 
                 CD30, CCR4, PDL1 
               
               
                 Molt-16 
                 RPMI, 20% FCS 
                 IL1ra, NKG2DNKG2D 
               
               
                 CEM 
                 RPMI, 10% FCS 
                 CD5 
               
               
                 MG-63 
                 DMEM, 10% FCS 
                 IL13RA2 
               
               
                 Karpass- 
                 RPMI, 20% FCS 
                 Alk, GPRC, PDL1 
               
               
                 299 
               
               
                 MCF7 
                 DMEM, 10% FCS 
                 B7D4, CD276, TROP2, Her3, Muc1, 
               
               
                   
                   
                 LewisY, LHR 
               
               
                 AA-2 
                 RPMI, 10% FCS 
                 HIV1 env glycoprotein (gp120) 
               
               
                 HL2/3 
                 DMEM, 10% FCS 
                 HIV1 env glycoprotein (gp120) 
               
               
                 TF228.1.16 
                 DMEM, 10% FCS 
                 HIV1 env glycoprotein (gp120), CCR4 
               
               
                 TT 
                 DMEM, 10% FCS 
                 TGF-Beta, TSHR, GFRalpha4 
               
               
                 DMS79 
                 RPMI, 10% FCS 
                 Fucosyl-GM1, Slea (CA19.9; Sialyl 
               
               
                   
                   
                 Lewis Antigen) 
               
               
                 LAN-5 
                 DMEM, 10% FCS 
                 ALK, DLL3, GFRalpha4, FUCOSYL-GM1 
               
               
                 PEER1 
                 RPMI, 10% FCS 
                 TSHR 
               
               
                 SK-MEL-37 
                 DMEM, 10% FCS 
                 DLL3, GD2 
               
               
                 F9 
                 DMEM, 10% FCS 
                 SSEA 
               
               
                 HepG2 
                 DMEM, 10% FBS 
                 GPC3, AFP/HLA-A2 
               
               
                   
               
            
           
         
       
     
     Jurkat cell line (clone E6-1) engineered with a NFAT-dependent EGFP (or GFP) reporter gene was a gift from Dr. Arthur Weiss at University of California San Francisco and have been described to study CAR-signaling ((Wu, CY et al., Science 350:293-302,2015). Jurkat cells were maintained in RPMI-1640 medium supplemented with 10% FBS, penicillin and streptomycin. 
     Generation of Lentiviral Vectors Encoding Chimeric Antigen Receptors against MPL 
     The pLENTI-Blast vector was derived from pLenti6v5gw_lacz vector (Invitrogen; ThermoFisher Scientific) by removal of the LacZ gene. pLenti-MP2 was a gift from Pantelis Tsoulfas (Addgene plasmid # 36097) and was used to generate pLenti-EF1α or pLenti-EF1α [SEQ ID NO:3837] lentiviral vector by replacement of the CMV promoter with human EF1α promoter using standard molecular biology techniques. pLenti-EF1a-DWPRE [SEQ ID NO:3838] was derived from the pLENTI-EF1α vector by deletion of WPRE sequence. An internal Sac II fragment was deleted from the EF1a promoter to generate EFlalpha (EF1a)-D-SACII-Promoter (SEQ ID NO: 3842). The psPAX2 vector was a gift from Didier Trono (Addgene plasmid # 12260). The pLP/VSVG envelope plasmid and 293FT cells were obtained from Invitrogen (ThermoFisher Scientific). The retroviral transfer vector MSCVneo, MSCVhygro, and MSCVpac and the packaging vector pKAT were obtained from Dr. Robert Illaria&#39;s laboratory. phRGTK Renilla Luciferase plasmid was from Promega. 
     The generation of Chimeric antigen receptor containing vectors with BBz, CD28z and z-K13 backbones, the generation and use of GGS-NLuc fusion proteins, and the generation and use of luciferase (e.g., GLuc) reporter cell lines for measurement of cellular cytotoxicity using the Matador assays have been described (PCT/US2017/024843, PCT/US2017/025602 and PCT/US2017/052344). 
     Lentivirus and Retrovirus Vectors 
     Lentiviruses were generated by calcium phosphate based transfection in 293FT cells essentially as described previously (Matta H et al, Cancer biology and therapy. 2(2):206-10. 2003). 293FT cells were grown in DMEM with 10% FCS 4 mM L-Glutamine, 0.1 mM MEM Non-Essential Amino Acids, and 1 mM MEM Sodium Pyruvate (hereby referred to as DMEM-10). For generation of lentivirus, 293FT cells were plated in 10 ml of DMEM-10 medium without antibiotics in a 10 cm tissue culture plate so that they will be approximately 80 confluent on the day of transfection. The following day, the cells were transfected by calcium phosphate transfection method using 10 μg of lentiviral expression plasmid encoding different genes, 7.5 μg of PSPAX2 plasmid and 2 μg of PLP/VSVG plasmid. Approximately 15-16 hours post-transfection, 9 ml of media was removed and replaced with 5 ml of fresh media. Approximately, 48 hours post-transfection, 5 ml of supernatant was collected (first collection) and replaced with fresh 5 ml media. Approximately 72 hrs post-transfection, all media was collected (second collection, usually around 6 ml). The collected supernatants were pooled and centrifuged at 1000 rpm for 1 minute to remove any cell debris and non-adherent cells. The cell-free supernatant was filtered through 0.45 pm syringe filter. In some cases, the supernatant was further concentrated by ultra-centrifugation at 18500 rpm for 2 hours at 4oC. The viral pellet was re-suspended in 1/10 of the initial volume in XVIVO medium. The virus was either used fresh to infect the target cells or stored frozen in aliquots at −80° C. 
     Infection of T cells and PBMC 
     Buffy coat cells were obtained from healthy de-identified adult donors from the Blood Bank at Children Hospital of Los Angeles and used to isolate peripheral blood mononuclear cells (PBMC) by Ficoll-Hypaque gradient centrifugation. PBMC were either used as such or used to isolate T cells using CD3 magnetic microbeads (Miltenyi Biotech) and following the manufacturer&#39;s instructions. PBMC or isolated T cells were re-suspended in XVIVO medium (Lonza) supplanted with 10 ng/ml CD3 antibody, 10 ng/ml CD28 antibody and 100 IU recombinant human-IL2. Cells were cultured at 37° C., in a 5% CO2 humidified incubator. Cells were activated in the above medium for 1 day prior to infection with lentiviral vectors. In general, primary cells (e.g. T cells) were infected in the morning using spin-infection (1800 rpm for 90 minutes at 37° C. with 300 μl of concentrated virus that had been re-suspended in XVIVO medium in the presence of 8 μg/ml of Polybrene® (Sigma, Catalog no. H9268). The media was changed in the evening and the infection was repeated for two more days for a total of 3 infections. After the 3rd infection, the cells were pelleted and resuspended in fresh XVIVO media containing 10 ng/ml CD3 antibody, 10 ng/ml CD28 antibody and 100 IU recombinant human-IL2 and supplemented with respective antibiotics (if indicated) and place in the cell culture flask for selection, unless indicated otherwise. Cells were cultured in the above medium for 10-15 days in case no drug selection was used and for 20-30 days in case drug-selection was used. In cases, where cells were infected with a lentivirus expressing EGFP, they were expanded without drug-selection or flow-sorted to enrich for EGFP-expressing cells. For infection of cancer cell lines, approximately 500,000 cells were infected with 2 ml of the un-concentrated viral supernatant in a total volume of 3 ml with Polybrene® (Sigma, Catalog no. H9268). Then next morning, the cells were pelleted and resuspended in the media with respective antibiotics and place in the cell culture flask for selection. 
     Essentially a similar procedure as described above for lentivirus vector production was used for generation of retroviral vectors with the exception that 293FT cells were generally transfected in 10 cm tissue culture plates in 10 ml of DMEM-10 medium using 10 μg of retroviral construct, 4μg of pKAT and 2μg of VSVG plasmid. The virus collection and infection of target cells was carried out essentially as described above for lentiviral vectors. 
     Antibodies and Drugs 
     Blinatumomab was obtained from Amgen. Digitonin was purchased from Sigma (Cat. no D141) and a stock solution of 100mg/ml was made in DMSO. A diluted stock of 1 mg/ml was made in PBS. Final concentration of digitonin used for cell lysis was 30 μg/ml unless indicated otherwise. 
     ELISA 
     Human IL2, IFNγ, IL6 and TNFa were measured in the cell culture supernatant of CAR-expressing Jurkat-NFAT-GFP effector cells or T cells that had been co-cultured with the specific target cell lines for 24 to 96 hours using commercially available ELISA kits from R&amp;D systems (Minneapolis, Minn.) and BD Biosciences and following the recommendations of the manufacturer. 
     FACS Analysis for Detecting Expression of CAR 
     Mouse Anti-Human c-Myc APC-conjugated Monoclonal Antibody (Catalog # IC3696A) was from R&amp;D Systems (Minneapolis, Minn.). Biotinylated protein L was purchased from GeneScript (Piscataway, NJ), reconstituted in phosphate buffered saline (PBS) at 1 mg/ml and stored at 4° C. Streptavidin-APC (SA1005) was purchased from ThermoFisher Scientific. 
     For detection of CARs using Myc staining, 1×10 6  cells were harvested and washed three times with 3 ml of ice-cold 1×PBS containing 4% bovine serum albumin (BSA) wash buffer. After wash, cells were resuspended in 0.1 ml of the ice-cold wash buffer containing 10 μl of APC-conjugated Myc antibody and incubated in dark for 1 hour followed by two washings with ice cold wash buffer. 
     For detection of CARs using Protein L staining, 1×10 6  cells were harvested and washed three times with 3 ml of ice-cold 1×PBS containing 4% bovine serum albumin (BSA) wash buffer. After wash, cells were resuspended in 0.1 ml of the ice-cold wash buffer containing 1 μg of protein L at 4° C. for 1 hour. Cells were washed three times with ice-cold wash buffer, and then incubated (in the dark) with 10μl of APC-conjugated streptavidin in 0.1 ml of the wash buffer for 30 minutes followed by two washings with ice cold wash buffer. FACS was done using FACSVerse analyzer from BD Biosciences. 
     Cell Death Assay 
     To measure cell death, a novel assay based on ectopic cytosolic expression of Gluc, NLuc and other luciferases was utilized as described in PCT/US2017/052344 “A Non-Radioactive Cytotoxicity Assay”. The method involves expression of a reporter in a target cells in a manner so that it is preferentially retained within the healthy cells but is either released from dead and dying cells or whose activity can be preferentially measured in dead and dying cells. The preferred reporter for this assay are 1) non-secreted forms of luciferases from the copepods, such as Gaussia princeps, 2) engineered luciferase reporters from deep sea shrimp, such as NanoLuc. The sequence of several such exemplary reporter vectors is provided in SEQ ID NO: 3845 to SEQ ID NO: 3851. The above vectors were used to generate retrovirus and lentiviruses which in turn were used to generate polyclonal population of several target cell lines stably expressing GLuc, NLuc, or TurboLuc following selection with appropriate antibiotics. Unless indicated otherwise, the target cells stably expressing the different luciferases were plated in triplicate in a 384 well plate in the media used for growing the target cells. Target cells which grow in suspension were generally plated at a concentration of 2-3×10 4  per well, while target cells which grow as adherent monolayers were plated at a concentration of 1-2×10 4  per well. Unless indicated otherwise, the target cells were cocultured with the genetically modified T cells (i.e. those expressing CAR) at an Effector: Target (E:T) ratio varying from 1: 1 to 10:1 for 4 hours to 96 hours. In the case target cells grow as adherent cells (e.g., HeLa cells), they were allowed to attach to the bottom of the wells overnight before the T cells were added. T cells mediated induction of lysis of target cells was assayed by increase of luciferase activity as measured by BioTek synergy plate reader by directly injecting 0.5 x CTZ assay buffer containing native coeloentrazine (Nanaolight) as described below. 
     CTZ Assay 
     A 100X stock solution of native coelenterazine (CTZ; Nanolight, cat # 303) was made by dissolving 1mg of lyophilized CTZ powder in 1.1 ml of 100% Methanol supplemented with 30 μl of 6N HCl to avoid oxidation of CTZ with time. To make CTZ assay buffer, the 100X stock solution of CTZ was diluted to 0.5X concentration in PBS. Unless indicated otherwise, a total volume of 15μl of the CTZ assay buffer (as prepared above) was added to each well of a 384-well white plate (Greiner, 384 well white plate cat # 781075) containing cells expressing the non-secretory form of the luciferase in approximately 50-60μl volume of medium and plates were read for luminescence using BioTek synergyH4 plate reader. For 96 well plates, cells were plated in 200 μl of media and approximately 50μl of 0.5X CTZ assay buffer was added. Unless indicated otherwise, the 0.5X CTZ assay buffer was used for assaying the activity of GLuc, TurboLuc16, and MLuc7. The CTZ assay buffer (diluted to 0.125X concentration) was also used for measurement of NLuc activity in some experiments. In general, unless indicated otherwise, the volume of 0.5X CTZ assay buffer added was approximately 1/4th of the volume of the liquid in the well containing the cells, although the assay also worked when the 0.5X CTZ assay was added to the media containing the cells in 1:1 volume. Gluc activity in wells containing media alone (Med) and in wells in which target cells were incubated with T cells that were not infected with any CAR construct (T-UI) were used as controls, where indicated. 
     Assay to detect the expression of antigens on target cells and to determine the antigen binding activity of various of antigen bindng moieties used in the construction of the CARs and BiTes 
     The expression of antigens on target cells was determined by bioinformatics approaches in combination with immunostaining with antigen specific antibodies or a highly sensitive antigen detection assay as described in PCT/US2017/025602 and incorporated herein in its entirety by reference. This assay involves the fusion of a GLuc or NLuc reporter fragment tot the antigen binding domain of an antibody, a scFv, a vHH or any other antigen binding fragment or any receptor and ligand. The resulting fusion protein is incubated with the target cells expressing the test antigen and the binding of the fusion protein is determined by addition of coelentrazine or other suitable substrate of the luciferase reporter. 
     Generatiton of a Diverse Pool of CAR T cells 
     The above assays were used to screen the different antigen binding modules (e.g. scFv, vHH, receptors, ligands) used in the construction of the CARs of this invention and the antigen binding modules that were found to show specific binding activity were selected for construction of the CARs. Furthermore, some of the scFV fragments were also selected based on their known activity in the literature or in our laboratory. 
     It is possible that different CARs or subset of CARs are optimally suited for different disease conditions depending on various factors including, but not limited to, the prevelance and level of expression of the target antigen on disease causing and disease-associted cells, disease burden and rate of progression of the disease. Different CARs may be optimally suited even for a single disease condition in different patients depending on their efficacy and toxicity profile and the condition of the patient. The disclosure provides a solutioin to the significant technical and logistical hurdles to generating a diverse adoptive immune response. 
     Normal TCR diversity is produced by gene rearrangement. Rigorous positive and negative selection processes in the thymus ensure that only T cells expressing the αβ TCR that are restricted to recognizing self-peptides/MHC within a low affinity range can populate the periphery. Thus, the thymic environment allows the generation of a pool of αβ T cells that are self-restricted, but not self-reactive. 
     Generating a diverse pool of CAR-T cells from different antigen binding domains is limited by the technical and financial hurdles of generating and testing multiple antigen binding domains. More importantly, as each of the antigen binding domains (e.g., vL and vH fragments of an antibody) has a potential of binding other antiges and causing off-target toxicity, a diverse pool of CARs based only on a plurality of antigen binding domains potentially has an increased risk of toxicity. Therefore, the potential diversity of such a pool would have to be limited to reduce off-target toxicity. The current disclosure overcomes this problem by generating a diverse pool of CARs from a single or a few antigen binding domains by attaching them to different variants of TCR chains, signaling domains and backbones. The diversity of the CARs pool is further increased by the use of different linkers. The diversity of T cells expressing the pool can be further increased by use of different accessory modules described in the disclosure. 
     This diverse pool of CARs can be used to provide a diverse immune response against disease causing or disease associated cells expressing the said antigen. Alternatively, the diverse pool of CARs can be optionally DNA barcoded using techniques known the art and subsequently used to select a single or a subgroup of CARs with optimal biological and clinical characteristics. These chacateristics may include but are not limited to, performance in the in vitro biological assays (e.g., cytotoxicity, cytokine secretion, binding affinity, cell surface expression, off-target effects, T cell proliferation, expression of exhaustion markers and terminal differentiation etc.), performance in the in vivo assays (e.g., survival, tumor reduction, T cell persistence, T cell expansion etc.) and clinical experience (e.g., disease remission, relapse rate, toxicities, etc.). The CARs of the disclosure can be used singly or in combination with other CARs and other natural and synthetic immune receptors known in the art to generate a diverse pool of immune effector cells for the prevention and treatment of various disease conditions caused by or associated with cells expressing their target antigens. 
     Use of in vitro and vivo selection to select CARs with desired properties. A pool of CARs targeting CD19 (SEQ ID NO: 1594-1608, 1016-1026, 1900-1910) are targeted to the TRAC locus in T cells using TRAC gRNA and techniques known in the art. The targeting vector also carry DNA barcodes located downstream of the stop codon of the CAR inserts. T cells can be derived from peripheral blood. In an alternate embodiment, T cells are derived from a single clone of iPSC or hematopoietic stem cells using techniques known in the art. T cells expressing the pool of CARs are co-cultured with RAJI cells in vitro for 1 to 21 days. Aliquotes of the CAR-T cell pools are collected before the culture with the target cells and on different days after co-culture. Samples are subjected to next generation sequencing to determine the relative frequency of different CARs following exposure to the target cells. Bioinformatics analyses is used to determine the CARs that are associated with better proliferative response following co-culture with the target cells. Essentially a similar approach is used to determine the CARs that confer higher proliferative potential on T cells in vivo and/or persist long term in vivo and/or are present at higher frequency when normalized for their frequency in the starting T cell population in surviving animals as compared to animals that succumb to tumor challenge. In alternate embodimentof the disclosure, essentially a similar approach is used on human clinical samples to identify CARs that are associated with different properties and/or outcomes including but not limited to better long term survival, lower incidence of cytokine release syndrome, lower neurotoxicity and/or higher long term persistence. Such CARs can be subsequently used, either singly or in various combinations, to develop different CARs subpools, containing CARs targeting the same or different antigen binding domains, with diverse properties for the treatment of different disease conditions and different patients. In other enablements, the CAR-T cells are exposed to their target cell line and then sorted into different sets based on the degree of intracellular IFNy as determined by flow cytometry. The frequency of different CARs in the low vs high IFNy population is determined by next generation sequencing and normalized to their frequency in the control CAR-T cell population, i.e., CAR-T cells that have not been exposed to the target cell line or are exposed to a cell line that does not express the targe of CARs. From this analysis, CARs that are associated with different levels of IFNy production can be determined. A similar approach is used to screen for and select CARs with any or a combination of desired properties or attributes including but not limited to, lower expression of exhaustion markers, lower expression of markers of terminal differentiation and/or higher expression of markers of cytotoxicity. 
     Use of MEMO-Mutants to Provide Costimulation 
     The mouse NEMO-K270A (SEQ ID NO: 992) is known to activate NF-κB constitutively. To demonstrate the ability of this mutant to provide costimulation to T cells, CD3+ve T cells were cultured in XVIVO medium (Lonza) supplanted with 10 ng/ml soluble anti-CD3, 10 ng/ml soluble anti-CD28 and 100 IU recombinant human-IL2. Cells were cultured at 37° C., in a 5% CO2 humidified incubator, and after 1 day infected with a lentiviral vector (pLENTI-EGFP-Blasticidin) expressing EGFP and lentiviral vectors expressing mouse NEMO-K270A mutants (pLENTI-mNEMO-K270A-FLAG-Blasticidin and pLENTI-mNEMO-K270A-HA-Blasticidin), or mouse NEMO-wt (pLENTI-mNEMO-FLAG-Blasticidin). The sequences of mNEMO-K270A and mNEMO-wt are provided in SEQ ID NOs: 992 and 991, respectively. Approximately lday post-infection, cells were selected with blasticidin and cell numbers calculated periodically. T cells infected with lentiviruses encoding the mouse NEMO-K270A mutants (pLENTI-mNEMO-K270A-FLAG-Blasticidin and pLENTI-mNEMO-K270A-HA-Blasticidin) were shown to proliferate more vigorously as compared to T cells infected with lentiviruses encoding EGFP or mouse NEMO-wt (pLENTI-mNEMO-FLAG-Blasticidin). 
     The human NEMO is longer than mouse NEMO and human NEMO-K277A (hNEMO-K277A; SEQ ID NO: 979) mutant corresponds to mouse NEMO-K270A (mNEMO-K270A) mutant. To test whether hNEMO-K277A mutant also activates NF-κB, expression vector (pCDNA3) encoding this mutant were generated. In addition, expression constructs encoding several other mutants of hNEMO in which Lys (K) at amino acid residue 277 was replaced by different amino acid residues (e.g., K277Q, K277T, K2771, K277N, K277S, K277M, K277G, K277R were generated). The different constructs were transfected in 293FT cells along with an NF-κB-Luciferase reporeter construct and a RSV-LacZ (normalization control) reporter construct and tested for their ability to activate NF-κB using assay described previously.  FIG.  3    shows strong activation of NF-κB by mNEMO-K270A, hNEMO-K277A and weak activation by hNEMO-K2771 and hNEMO-K277G mutant. In a similar experiment, the hNEMO-K277L and hNEMO-K277A-DeltaV249-K255 mutants also showed NF-κB activation when transfected into 293FT cells. The hNEMO-K277A-DeltaV249-K255 mutant lacks the aminoacid residues V249-K255 of human NEMO and also carries the K277A mutation. These results suggest that constitutive active mutants of NEMO can be rapidly generated and identified by mutating mouse NEMO K270 residue and human NEMO K277 residue. A similar approach can be used to generate mutants at other NEMO residues that have the ability to activate NF-κB. 
     FMC63 based CD19 CAR CAR construct were generated that coexpressed wither full length hNEMO-K277A or hNEMO-L753 mutant (encoding amino acids 1-251) in fusion with an N-terminal FKBPx2 dimerizer domain. The constructs were transfected into 293FT cells along with an NF-κB-Luciferase reporeter construct and a RSV-LacZ reporter construct. Approximatley 8 hours, post-transfection, cells were left untreated or treated with AP20187 (100 nM). After approximately 72 hours, cell lysates were prepared and analyzed for NF-κB luciferase and LacZ activities as described previously. NF-κB-Luc activity was normalized for LacZ activity to control for difference in transfection efficiency. Results showed that treatment with AP20187 led to increase in NF-κB activity in 293FT cells transfected with CAR encoding constructs co-expressing both FKBPx2-hNEMO-K277A (SEQ ID NO: 1006) and FKBPx2-hNEMO-L753 (SEQ ID NO: 1007) mutants. These results demonstrate the ability to activate NF-κB in an inducible manner in a CAR or TCR or chimeric TCR construct by coexpression of full length NEMO or its deletion mutants in fusion with a dimerizer domain followed by addition of a dimerizer. 
     J-N-G cells are infected with CD19-directed FMC63 based 1 st  generation CARs coexpressing FKBPx2-hNEMO-K277A or FKBPx2-hNEMO-L753. Cells are cocultured with RAJI target cells in the absence and presence of AP20187 compound and shown to induce EGFP expression, demonstrating that FKBPx2-hNEMO-K277A or FKBPx2-hNEMO-L753 can be co-expressed with a CAR without interfering with its activity. 
     In addition to NEMO, a number of other cellular proteins are known to activate NF-κB constitutively and can be used in alternate embodiment of the invention to provide costimulation to T cells for the purpose of adoptive cellular therapies. Exemplary proteins include TCL-1A (SEQ ID NO: 1005) and constitutive active mutants of IKKa/IKK1 (IKK1-5176E-S180E; SEQ ID NO: 1004), IKKβ/IKK2 (IKK2-S177E-S181E; SEQ ID NO: 1002) and MYD88-L265P (SEQ ID NO: 1000). In an embodiment embodiment, these proteins are expressed without a dimerizer domain to provide constitutive costimulation to T cells for the purpose of adoptive cellular therapy. These proteins can be expressed in the T cells using any vector (e.g., lentiviral, retroviral, AAV or sleeping beauty transposon vectors) or non-vector (DNA or RNA transfection) method of gene delivry known in the art. Alternatively, these proteins can be expressed by alteration of their genomic copies using techniques of gene altering (e.g., Cas9, Talons, Zn finger nucleases) known in the art. In an exemplary embodiment, one or more genomic copies of hNEMO are mutated to hNEMO-K277A using homologous recombination in T cells using techniques known in the art. 
     The expression of these costimulatory proteins can be controlled by expressing them using inducible promoters known in the art, such as Tet-inducible promoter or RheoGene system. In an embodiment, hNEMO-K277A mutant and hNEMO-K277A-DeltaV249-K255 are cloned in the pSLIK-Tet-On vector (Gopalakrishnan et al, Clinical Cancer Res; 19(18), 2013) and the resulting virus is used to infect T cells. Treatment of T cells with doxycycline is shown to induce hNEMO-K277A and hNEMO-K277A-DeltaV249-K255 expression and NF-κB activity. NF-κB activity is measured by AlexaFlour-conjugated Phospho-IκBα antibody and flow cytometry. 
     In alternate embodiements of the invention, other NF-κB activating proteins or their signaling domains (e.g., IKK1, IKK2, RIP, etc.) are expressed as fusion with a dimerizer domain to provide costimulation to T cells in an inducible manner. The use of these constitutive or inducible NF-κB activating proteins of the invention is not limited to providing costimulation to T cells as they can be used to provide costimulation to other immune cells (e.g., NK cells, dendritic cells, antigen presenting cells etc.) where NF-κB activation is known to enhance their function. As NF-κB is known to protect against apoptosis and promote cell survival, these constitutive and inducible NF-κB activating proteins can be also used in cell engineering to enhance the survival of cells used in biological products manufacturing. In an exemplary embodiment, hybridoma cells are engineered to express hNEMO-K277A, hNEMO-K277A-DeltaV249-K255 (SEQ ID NO: 7769), K13, IKKa/IKK1 (IKK1-SS/EE; SEQ ID NO: 1004), IKKβ/IKK2 (IKK2-S177E-S181E; SEQ ID NO: 1002) or MYD88-L265P (SEQ ID NO: 1000) constitutively to enhance their proliferation and ability to grow at high cell density. 
     NF-κB activators for T cell adoptive cell therapy. 
     Buffy coat cells are obtained from healthy de-identified adult donors from a Blood Bank and used to isolate peripheral blood mononuclear cells (PBMC) by Ficoll-Hypaque gradient centrifugation. T cells are isolated using CD3 microbeads (Miltenyi), cultured in XVIVO 15 medium supplemented with CD3/CD28 Dynabeads and 50 IU/ml of recombinant IL2. Alternatively, T cells are re-suspended in XVIVO medium (Lonza) supplanted with 10 ng/ml CD3 antibody, 10 ng/ml CD28 antibody and 100 IU recombinant human-IL2. 
     Next day, T cells are infected with CD19-targeted CARs (including next generatiton CARs)-encoding lentiviral vectors in the pCCL3-MND3 backbone. The nucleic acid sequences of the CARs are shown in SEQ ID NO: 1016-1029, 1318-1331, 1594-1604, 1900-1913, 2206-2219, 2512-2525, 2818-2831, 3124-3127, 3324-3327. In addition, T cells are infected with CAR constructs corresponding to the above constructs but which lacked the hNEMO-K277A module. For each infection, 18 million T cells are infected with 500 μl of concentrated viruses encoding the different CAR constructs and 8 μg/m1Polybrene by spinfection at 2800 rpm, 32° C. for 90 min in 6-well plates. The plates are incubated at 37° C. for 6 hours. The cells are collected, centrifuged to remove virus and Polybrene, resuspended in fresh culture medium and cultured overnight at 37° C. 
     Next day, spinfection is repeated and cells are transferred to T-75 cell culture flasks with XVIVO 15 medium supplemented with CD3/CD28 Dynabeads, 50IU/m1IL2 and 5% FBS. 
     After 4 days of expansion, CAR—T cells are checked for CAR expression using Protein L staining, CD19-binding, cytokine production (IL2, IFNγ, TNFa) and cytotoxicity (Matador assay). 
     After 10 days of expansion, the CAR/SIR-T cells are used for in vivo experiment. For this purpose, NSG mice are injected with 10 6  Nalm-6-Luc cells via tail vein injection. Two days later, 3x 10 6  CAR/SIR-T cells injected. Mice are imaged weekly by bioluminescence imaging following administration of D-Luciferin and followed for survival. 
     It is noted that T cells expressing the first generation CARs along with hNEMO-K277A (SEQ ID NO: 1594-1604) show superior IL2 production as measured by ELISA when exposed to RAJI cells as compared to T cells expressing 2 nd  generation CARs (SEQ ID NO: 1594-1604) with a BBz costimulatory domain. In addition, T cells expressing the first generation CARs along with hNEMO-K277A (SEQ ID NO: 1594-1604) show less signs of exhaustion as measured by cell proliferation, cytokine (IL2, IFNγ, TNFa) production, expression of exhaustion markers (e.g., PD1) and cytotoxicity (Matador cytotoxicity assay) when cocultured with RAJI cells over 3 weeks period as compared to T cells expressing 2 nd  generation CARs (SEQ ID NO: 1594-1604) with a BBz costimulatory domain. Finally, T cells expressing the first generation CARs along with hNEMO-K277A (SEQ ID NO: 1594-1604) show superior in vivo activity when administered to NSG mice xenografted with NALM-6-Luc cells as determined by T cells expansion and persistence in vivo, reduction in tumor growth and improved survival. The T cells expressing the first generation CARs along with hNEMO-K277A (Backbone 2; SEQ ID NO: 1594-1604) in general show weaker production of cytokines (e.g., IL2, IFNy and TNFa) when exposed to RAM cells as compared to T cells expressing first generation CARs and coexpressing vFLIP K13 (i.e., Backbone 1; SEQ ID NO: 1016-1029). 
     T cells expressing the CAR constructs corresponding to SEQ ID NO: 1900-1913, 2206-2219, 2512-2525, 2818-2831, 3124-3127, 3324-3327 which express hNEMO-K277A show superior in vitro and in vivo activity as compared to the T cells expressing similar constructs but which lack the hNEMO-K277A module. Co-expression of hNEMO-K277A module is also shown to improve the in vitro and in vivo performance of T cells expressing a SIR (SEQ ID NO: 9683) targeting CD20. These results demonstrate that the coexpression of hNEMO-K277A accessory module enhances the in vitro (e.g., proliferation, cytokine production, delay of exhaustion) and in vivo activity (e.g., improved expansion of T cells and anti-tumor activity) of not only the first generation CAR constructs but also of TFP, Ab-TCR and SIRs. 
     A difference is also noted among the different constructs containing the same backbone but having different antigen binding domains. Thus, among the first generation CAR constructs coexpressing hNEMO-K277A (i.e. Backbone 2) constructs containing the antigen binding domain derived from 4G7 (e.g., SEQ ID NO:1599), huBly3 (e.g., SEQ ID NO: 1604), and huSJ25C1 (e.g., SEQ ID NO: 1605) scFV are generally weaker as compared to constructs containing the antigen binding domain derived from scFv based on FMC63 (e.g., SEQ ID NO: 1594), hu-FMC63-11 (e.g., SEQ ID NO: 1595), huFMC63-11-N203Q (e.g., SEQ ID NO: 1596), Bu12 (e.g., SEQ ID NO: 1597), CD19-MOR0028 (e.g., SEQ ID NO: 1602) and CD19-hu-mROO5 (e.g., SEQ ID NO: 1607). A similar trend is observed in the in vitro and in vivo activity of CARs on other backbones based on the nature of their antigen binding domains. 
     In the preceding experiments, the hNEMO-K277A module is co-expressed with the CAR module in the T cells using a single vector. The experiment is repeated in which the two modules are expressed using two separate lentiviral vectors. The SEQ ID of nucleic acid construct encoding an exemplary CD20 CAR lacking a hNEMO-K277A module is presented in SEQ ID: 9668. T cells are coinfected with the two lentiviral vectors at multiplicity of infection of 5 and the ratio fo the two vectors (i.e. CAR:hNEMO-K277A) is varied from 1:1 to 1:10. The T cells are expanded and tested in the in vitro and in vivo assays. Co-expression of hNEMO-K277A along with a CAR construct is shown to improve the in vitro and in vivo performance of CAR-T cells as determined by assays for IL2 production, cell proliferation, lack of exhaustion, in vivo expansion and anti-tumor activity. 
     In an alternate embodiment, homologous recombination using gene editing techniques known in the art (e.g., CRISP/Cas9, TALON, Zn finger nucleases etc.) is used to induce the K277A mutation in one or both copies of the endogenous human NEMO gene in T cells. The resulting T cells carrying the hNEMO-K277A mutation are then used for adoptive cellular therapy, including to express the CAR constructs targeting CD19 and TCR constructs targeting NY-ESO-1. The T cells carrying the hNEMO-K277A mutations are shown to show enhanced proliferation, cytokine production, expansion, long term persistence in vivo and anti-tumor activity as compared to control T cells lacking the hNEMO-K277A mutation. 
     The experiments described in the preceding paragraphs are repeated by using CAR constructs in which the hNEMO-K277A accessory module is replaced by accessory modules encoding FKBPx2-hNEMO, FKBPx2-hNEMO-K277A (SEQ ID NO: 1006), FKBPx2-hNEMO-L753(251) (SEQ ID NO: 1007), FKBPx2-hNEMO-L600(200) (SEQ ID NO: 1008), IKK2-delta-SCD-FKBPv36x2 (SEQ ID NO: 7782), IKK1-delta-SCD-FKBPv36x2 (SEQ ID NO: 7781) and FKBPx2-RIP-ID (SEQ ID NO: 1009). T cells expressing the CAR and these accessory modules are tested using in vitro assays in the absence and presence of the dimerizer AP20187 (100nM). Addition of AP20187 is shown to induce the proliferation and cytokine production by CAR-T cells expressing the FKBPx2-hNEMO, FKBPx2-hNEMO-K277A (SEQ ID NO: 1006), FKBPx2-hNEMO-L753(251) (SEQ ID NO: 1007), IKK2-delta-SCD-FKBPv36x2 (SEQ ID NO: 7782), IKK1-delta-SCD-FKBPv36x2 (SEQ ID NO: 7781), FKBPx2-hNEMO-L600(200) (SEQ ID NO: 1008) and FKBPx2-RIP-ID (SEQ ID NO: 1009) modules when exposed to target antigen (i.e., CD19) expressing RAJI cells. In an in vivo experiment, NSG mice (n=12 per group) are xenografted with 2 million RAJI-Luc cells by tail vein injection and 3 days later administered 5 million T cells expressing a CD19-CAR and coexpressing the FKBPx2-hNEMO, FKBPx2-hNEMO-K277A (SEQ ID NO: 1006), FKBPx2-hNEMO-L753(251) (SEQ ID NO: 1007), FKBPx2-hNEMO-L600(200) (SEQ ID NO: 1008) and FKBPx2-RIP-ID (SEQ ID NO: 1009) modules. Half the mice in each group (n =6) are administered 40 μg of AP20187 every day for 10 days by intraperitoneal injection as described previously (Chinnery et al, J Immunol 2009; 182:2738-2744). Administration of AP20187 is shown to promote the expansion of CAR-T cells. In an alternate embodiment, the experiment is repeated using constructs in which both the FKBP domains carry the FKBP12V36 mutation which bind to the lipid-permeable dimerizing ligand, Rimiducid, at high affinity. Dimerization of the fusion proteins is brought by administration of rimiducid. For in vitro experiments, Rimiducid is used at final concentration of 10-100nM. For in vivo studies in NSG mice, Rimiducid is administered weekly by intraperitoneal (i.p) injection at 5 mg/kg. 
     The experiments described in the preceding paragraphs are repeated by using constructs in which the hNEMO-K277A accessory module is replaced by accessory modules encoding hNEMO-K277A-DeltaV249-K255, IKK2-S177E-S181E, IKK1-S176E-S180E, MYD88-L265P, TCL-1A, and MTCP-1. The CAR-T cells expressing the hNEMO-K277A-DeltaV249-K255, IKK2-S177E-S181E, IKK1-S176E-S180E, MYD88-L265P accessory modules are shown to demonstrate increased cytokine production, proliferation, in vivo expansion and anti-tumor activity as compared to CAR-T cells lacking the accessory module. The CAR-T cells expressing the TCL-1A and MTCP-1 accessory module are shown to have increased proliferative response. 
     Use of human NEMO-K277A, human NEMO-K277A-deltaV249-K255, mouse NEMO-K270A and IKK2-S177E-S181E in vaccination 
     Lentivral vectors are generated expressing human NEMO-K277A, human NEMO-K277A-deltaV249-K255, mouse NEMO-K270A and IKK2-S177E-S181E. Lentivral vectors are also generating expressing chicken ovalbumin amin acid residues 242-353 and the C terminus of the major histocompatibility complex (MHC) class II invariant chain (Ii-OVA) as described in Rowe HM et al, Molecular Therapy, 13, 2, 2006. Finally, lentiviral vectors are generated coexpressing a cassette encoding human NEMO-K277A, human NEMO-K277A-deltaV249-K255, mouse NEMO-K270A or IKK2-S177E-S181E with a cassette encoding Ii-OVA where the two cassettes are separated by a 2A cleavage sequence. 
     Transduction of DCs and flow cytometry. Murine bone marrow-derived Dendritic cells (DCs) are prepared as previously described. Immature DCs are transduced on day 4 at an MOT of 20 with lentiviral vectors as described (Rowe HM et al, Molecular Therapy, 13, 2, 2006) and fed every 4 days with fresh medium containing granulocyte-macrophage colony-stimulating factor (50 ng/ml; from Peprotech). On day 5 posttransduction, DCs are harvested, washed, and blocked for Fc receptors before surface staining for maturation markers with the following biotin-conjugated Abs: anti-CD11c, anti-CD86, and anti-I-Ab (MHC class II) (all from BD Pharmingen); anti-CD40 (from Serotec); and anti-CD80, anti-ICAM-1, and anti-Kb (MHC class I) (all from eBioscience). A hamster isotype control Ab (biotin conjugated) is purchased from BD Pharmingen. Abs are then labeled with streptavidin RPE Cy-5 2o reagent (DakoCytomation) before flow cytometry. Lipopolysaccharide (LPS) (50 ng/ml) (Sigma) is added to untransduced DCs and left overnight as a positive control for maturation. Zymosan A (10 μg/ml) treatment (for 30 min at 37° C.) is used as a control for ERK activation. 
     ELISA. Culture supernatants are harvested from DCs plated at 5×10 5  cells per well (in 1.5 ml). IL-12p70 and tumor necrosis factor alpha (TNF-a) are detected by sandwich enzyme-linked immunosorbent assay (ELISA), using kits from eBioscience according to the manufacturer&#39;s guidelines. 
     DC purification from lymph nodes. C57/BL6 mice (Harlan) are injected subcutaneously (s.c.) at the base of the tail with 1×10 8  infectious units (i.u.) lentivector. Six days later, lymph nodes (para-aortical and inguinal) are harvested (cells from mice in each group were pooled), incubated with collagenase CLS-4 (Worthington), and mashed to obtain single-cell suspensions. Fc receptors are blocked before CD11c-positive cells are selected using MACS beads (Miltenyi Biotec). 
     Pentamer staining. One million splenocytes per sample are incubated with 10 μl of phycoerythrin-conjugated SIINFEKL/Kb pentamer or tetramer (Proimmune) for 12 min at room temperature. The cells are then washed and incubated on ice with biotin-conjugated anti-CD8 (Serotec) for 15 min before being washed and incubated with streptavidin-allophycocyanin (eBioscience) for 15 min. Samples are washed and acquired on a BD LSR machine using Cell-Quest software (BD Biosciences). 
     Intracellular cytokine staining. Splenocytes are incubated overnight with or without OVA257-264 peptide. Monensin solution (eBiosciences; final concentration, 2 μM) is added and left for 3 h before surface staining cells for CD8. The cells are then fixed and permeabilized using a Cytofix/Cytoperm kit from BD Biosciences. An allophycocyanin-conjugated anti-gamma interferon (anti-IFN-y) Ab (BD Pharmingen) is then added and left for 30 min before the cells are washed and samples are run on a BD LSR machine. 
     ELISPOT assay. Enzyme-linked immunospot (ELISPOT) plates (Millipore) are coated overnight at 4° C. with purified anti-IFN-y (BD Pharmingen). Ex vivo ELISPOT assays is performed with serial dilutions of total splenocytes in triplicate with or without class I OVA257-264 peptide (Proimmune). Plates are cultured overnight and developed according to the manufacturer&#39;s directions. Spots are counted using an AID ELISPOT counter and software. 
     Tumor therapy. EG7.OVA tumor cells are grown in RPMI plus 0.4 mg/ml G418 (Invitrogen). C57BL/6 mice are challenged with 2×10 6  tumor cells injected s.c. into the flank and then vaccinated. Animals are killed once they had a tumor that reached a diameter of &gt;15 mm. 
     Mouse BM-derived Dendritic cells (DCs) are infected with the lentivectors encoding human NEMO-K277A, human NEMO-K277A-deltaV249-K255, mouse NEMO-K270A and IKK2-S177E-S181E either alone or in combination with Ii-OVA. Expression of human NEMO-K277A, human NEMO-K277A-deltaV249-K255, mouse NEMO-K270A and IKK2-S177E-S181E is shown to result in nuclear translocation of p65 (RelA) in the nuclei of the DCs at a level similar to that in the LPS-treated DCs but not in the untreated or control vector DCs, in which the level of cytoplasmic p65 is higher. Increased nuclear NF-κB binding activity is also detected in human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E-transduced DCs but there is no affect on the activation of the MAPK pathway as determined by nuclear AP1 binding activity. 
     After transduction of BM-derived DCs with human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E, maturation markers on the transduced or nontransduced cells are analyzed. CD86, CD40, ICAM-1, and CD80 are upregulated on human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E -expressing DCs compared to transduced DCs in the control vector group. Furthermore, human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E-transduced DCs are shown to retain their upregulated CD86 for several weeks in culture. The secretion of IL-12p70 and TNF-a is found to be upregulated in the culture of DCs transduced with human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E. 
     Following s.c. lentivector injection, transduced DCs are detected in the draining lymph nodes. A similar percentage of lymph node DCs (CD11c + /MHC class II + ) are transduced after s.c. injection with either the control or the human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E vector. However, there is an upregulation of CD86 on DCs in the human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E-injected animals compared to the control vector-injected animals. 
     The ability of vectors encoding human NEMO-K277A-2A-Ii-OVA, human NEMO-K277A-deltaV249-K255-2A-Ii-OVA, mouse NEMO-K270A-2A-Ii-OVA, IKK2-S177E-S181E-2A-Ii-OVA and Ii-OVA to induce an Ova-specific CD8 + T-cell response in mice after s.c. vaccination is examined. The vector dose of 5×10 5  i.u. is used. The human NEMO-K277A-2A-Ii-OVA, human NEMO-K277A-deltaV249-K255-2A-Ii-OVA, mouse NEMO-K270A-2A-Ii-OVA and IKK2-S177E-S181E-2A-Ii-OVA vaccinated mice show SIINFEKL/Kb pentamer-positive CD8 +  T cells and IFN-y-secreting CD8 +  T cells as measured by intracellular fluorescence-activated cell sorting or ELISPOT assay. 
     Mice are inoculated with a lethal dose of EG7.OVA tumor cells before vaccinating them either with transduced DCs or with the human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E-vectors directly. All mice are shown to develop tumors. After either transduced DC injection or direct lentivector injection, the number of tumor-free mice in the human NEMO-K277A-, human NEMO-K277A-deltaV249-K255-, mouse NEMO-K270A- and IKK2-S177E-S181E-group is higher than that in the control group. The efficacy of the NEMO-K277A-2A-Ii-OVA, human NEMO-K277A-deltaV249-K255-2A-Ii-OVA, mouse NEMO-K270A-2A-Ii-OVA, IKK2-S177E-S181E-2A-Ii-OVA vectors is tested in a parasite protection model (Polley R et al, Infect. Immun. 74:773-776, 2016) using L. donovani expressing ovalbumin. 
     Use of human NEMO-K277A, human NEMO-K277A-deltaV249-K255, mouse NEMO-K270A and IKK2-S177E-S181E in vaccination 
     Antigen presenting cells collected in a single leukapheresis are transduced with adenoviral vector encoding human NEMO-K277A, human NEMO-K277A-deltaV249-K255, mouse NEMO-K270A and IKK2-S177E-S181E, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. Men with progressive mCRPC following &lt;1 prior chemotherapy regimen are enrolled to evaluate three doses of the resulting vaccine (4×10 6 , 12.5×10 6  and 25×10 6  cells) administered intradermally every 2-4 weeks. There are no dose-limiting toxicities. Immune upregulation as well as anti-tumor activity are observed with PSA declines. 
     Construction and testing of humanized MPL CAR based on scFv fragment derived form 161 antibody 
     The murine monoclonal antibody 161 targets human MPL (Thrombopoietin receptor o TPO-R). To generate a CAR targeting MPL but with reduced immunogenicity, sequence of the scFV fragment comprising the antigen binding domain of the murine 161 antibody was humanized. The humanized 161 scFv fragment (SEQ ID NO: 891), designated hu-161-2, was cloned in the 2nd generation CAR backbone containing the 41BB costimulatory domain and CD3z activation domain (SEQ ID NO: 1582). Jurkat-NFAT-EGFP (J-N-G) cells were stably transduced with the lentivirus encoding the humanized MPL-hu-161-2 CAR construct. The parental and CAR-expressing Jurkats were subsequently cocultured with HEL cells and induction of EGFP expression monitored by FACS analysis after 4 h. Coculturing of Jurkat cells expressing MPL-hu-161-2 CAR construct with HEL cells led to increase in EGFP expression as compared to cells that had not been exposed to HEL cells, indicating the abilty of humanized MPL-hu-161-2 CAR construct to recognize the target antigen and activate signaling. Essentially similar results are obtained when the experiment is repeated with a first generation CARs incorporting hu-161-2 scFV and coexpressing either vFLIP K13 (SEQ ID NO: 1286) or hNEMO-K277A mutant (SEQ ID NO: 1878). 
     Construction and Testing of Humanized MPL CAR based on scFv Fragment Derived form 175 and 111 Antibody 
     The murine monoclonals 175 and 111 also bind human MPL. Therefore, the sequence of the scFV fragments comprising the antigen binding domain of these antibody is humanized and used to make the corresponding 2nd generation CAR (CAR II) constructs (SEQ ID NOs: 1583 and 1584) as well as backbones 1 and 2 coexpressing vFLIP K13 (SEQ ID NO: 1287, 1288) and hNEMO-K277A (SEQ ID NOs: 1896 and 1897). The experiment is repeated as in the preceding example. Co-culturing of Jurkat cells expressing MPL-hu-175-2 and hu-111-2 CAR constructs with HEL cells led to increase in EGFP expression as compared to cells that had not been exposed to HEL cells, indicating the abilty of humanized MPL-hu-175-2 and hu-111-2 CAR constructs to recognize the target antigen and activate signaling. 
     Construction and Testing of CARs Targeting CD70 
     A number of constructs targeting CD70 are constructed (SEQ ID NO: 9781-10086; and 7783-7789). The constructs are expressed in J-N-G and T cells and tested for T cell activation and cytotoxicity against CD70-expressing target cell lines RAJI and THP-1 using in in vitro and in vivo assays. 
     Construction and testing of CARs targeting CD70, PTK7, kappa light chain, Claudin18A2, Ras/HLA-A2 complex, NY-ESO/HLA-A2 complex, Streptag and an epitope of CD43 expressed on leukemia cells. 
     CAR constructs are generated targeting PTK7, kappa light chain, Claudin18A2, Ras/HLA-A2 complex, NY-ESO/HLA-A2 complex, Streptag and an epitope of CD43 expressed on leukemia cells on either a 2 nd  generation backbone (e.g., conventional CAR II) or backbones 1 and 2 co-expressing either vFLIP K13 or hNEMO-K277A. The experiment is repeated as in the preceding example. Coculturing of Jurkat cells expressing the different CAR constructs with their respective target cells led to increase in EGFP expression as compared to cells that had not been exposed to the target cells. Similarlty, coculturing of T cells expressing the different CAR constructs with their respective target cells expressing GLuc led to increase in cell death as measured by increase in GLuc activity. 
     TFP Targeting MPL 
     Several TFP based CARs are constructed targeting MPL based on hu-161-2 scFV as the antigen binding domain. The sequence of these TFP CAR constructs is shown in SEQ ID NO: 3526 to 3533. Jurkat-NFAT-EGFP (J-N-G) cells are transduced with lentiviruses encoding the TFP CARs targeting MPL and selected with puromycin. J-N-G cells expressing the TFP CARs targeting MPL are shown to induce EGFP expression upon co-culture with HEL.92.1.7 (HEL) cells for 4 hours. TFP CARs targeting MPL are also expressed in primary T cells and tested for their ability to induce lysis of HEL-GLuc cells upon co-culture for 4 hours. MPL TFP CAR constructs based on 175, 111, hu-175-2 and hu-111-2 scFv (SEQ ID NO: 10476-10483) are similarly constructed and tested using J-N-G and primary T cells as described above for hu-161-2 based TFP CARs. J 
     TFP Targeting other Antigens 
     Next TFP CARs targeting a number of different antigens are constructed. In order to provide costimulation, the constructs also coexpress hNEMO-K277A.Th e constructs are expressed in J-N-G and primary T cells and tested for their abilty to recognize cells expressing their target antigen using the assays described above. The TFP CARs expressing J-N-G cells are shown to induce EGFP expression upon co-culture with the target cell expressing their cognate antigen. T cells expressing these TFP CARs targeting different antigens are shown to induce cytotoxicity of the target cells expressing the corresponding antigen using the GLuc based cytotoxicity assay described above. Table A shows the target cell lines expressing the different target antigens that are used in the assay. Additional cell lines expressing the different target antigens are known in the art or can be genetically engineered to express a desired antigen by techniques known in the art. In the above example, the TFP constructs contain an accessory module that co-expresses hNEMO-K277A mutant to provide co-stimulation. In alternate embodiment, TFP constructs are also constructed that either lack an accessory module to provide costimulation or contain an accessory module which provides costimualtion through the co-expression of other proteins, such as vFLIP K13. The experiment is repeated as above by expression of the TFP constructs in J-N-G and primary T cells with similar results. 
     Ab-TCR Targeting MPL 
     Several Ab-TCR are constructed targeting MPL based on murine 161 scFV as the antigen binding domain. To imrove the expression of TCRα and TCRβ based Ab-TCR, specific mutations are introduced in their TCR receptor modules. The sequence of the TCRy/TCRd, wild-type TCRα/TCRβ (labelled wt-op2) and mutant TCRα/TCRβ (labelled SDVP-IAH) containing Ab-TCR constructs are shown in SEQ ID NO: 959 to 964. Jurkat-NFAT-EGFP (J-N-G) cells are transduced with lentiviruses encoding the Ab-TCRs targeting MPL (SEQ ID NO: 2091, 2397, 2703) and selected with puromycin. J-N-G cells expressing the Ab-TCRs targeting MPL are shown to induce EGFP expression upon co-culture with HEL cells for 4 hours, demonstrating the ability of Ab-TCRs targeting MPL to recognize MPL and activate signaling. Ab-TCRs targeting MPL are also expressed in primary T cells and tested for their ability to induce lysis of HEL-GLuc cells upon co-culture for 4 hours. T cells expressing MPL Ab-TCRs are shown to induce lysis of HEL-GLuc cells as measured by increase in GLuc activity. MPL Ab-TCR constructs based on murine 175 and 111 scFv (SEQ ID NO: 10492-10493) are similarly constructed and tested using J-N-G and primary T cells as described above for 161 based Ab-TCRs. 
     Ab-TCRs Targeting other Antigens 
     Next Ab-TCRs targeting a number of different antigens are constructed. In order to provide costimulation, the constructs also coexpress hNEMO-K277A. The constructs are expressed in J-N-G and primary T cells and tested for their abilty to recognize cells expressing their target antigen using the assays described above. The Ab-TCRs expressing J-N-G cells are shown to induce EGFP expression upon co-culture with the target cell expressing their cognate antigen. T cells expressing these Ab-TCRs targeting different antigens are shown to induce cytotoxicity of the target cells expressing the corresponding antigen using the GLuc based cytotoxicity assay described above. Table A shows the target cell lines expressing the different target antigens that are used in the assay. Additional cell lines expressing the different target antigens are known in the art or can be genetically engineered to express a desired antigen by techniques known in the art. In the above example, the Ab-TCR constructs contain an accessory module that co-expresses hNEMO-K277A mutant to provide co-stimulation. In alternate embodiments, Ab-TCR constructs are also constructed that either lack an accessory module to provide costimulation or contain an accessory module which provides costimualtion through the co-expression of other proteins, such as vFLIP K13. The experiment is repeated as above by expression of the Ab-TCR constructs in J-N-G and primary T cells with similar results. 
     Flow Cytometry for CAR-Mediated Proliferation of Transduced CD8+ T Lymphocytes in Response to HIV-1-Infected Target Cells 
     A number of CARs targeting HIV1 envelop glycoprotein are generated and are represented by SEQ ID NO: 8704-9349. The following assays are used to test their anti-HIV1 activity in vitro. The active constructs are used singly or in combination for the treatment of patients with HIV1 and AIDS. 
     HIV-1-infected T2 cells, which are MHC class I low due to a deletion in the transporter associated with processing (TAP) (Salter, et al. (1986) EMBO J 5:943-949) and previously shown to be suitable target cells for an HIV-1-specific CAR (Severino, et al. (2003) Virology 306:371-375), served as target cells. These are infected with an excess of HIV-1 NL4-3-based reporter virus containing a gene for murine CD24 (mCD24) in the vpr locus (Ali, et al. (2003) J Virol Methods 110: 137-142) to yield &gt;90% infected cells by 3 or 4 days after infection, as previously described (Bennett, et al. (2007) J Virol 81 :4973-4980; Yang, et al. (1996) J Virol 70:5799-5806; and Yang, et al. (1997) J Virol 71 :3120-3128). These are irradiated immediately before use with 10,000 rads in a cesium irradiator, as well as peripheral blood mononuclear cells from a healthy donor with 3,000 rads (feeder PBMCs). HIV1-CAR transduced primary CD8+ T lymphocytes are labeled with CellTrace Violet and washed according to manufacturer&#39;s directions (ThermoFisher Scientific, Grand Island, NY). In a 48 well plate well, 5×10 5  labeled transduced cells are added to 5×10 5  irradiated infected T2 cells and 2×10 6  irradiated feeder PBMCs, and cultured in 1 ml R10-50 for five days with a medium change after three days. Flow cytometry (LSR Fortessa II cytometer, BD Biosciences) was then performed with co-staining for human CD8 (PerCP-anti-human CD8, catalog #30130, Biolegend, San Diego, CA) and analysis of proliferation using FlowJo software (FlowJo, Ashland, OR). HIV1-CAR-transduced T cells are shown to proliferate when exposed to HIV-1-infected T2 cells. 
     Virus Suppression Assays 
     The ability of HIV1-CAR transduced CD8+ T lymphocytes and expanded and enriched clones thereof to suppress the replication of HIV-1 is tested as previously described (Yang, et al. (1997) PNAS USA 94: 11478-11483; and Yang, et al. (1997) J Virol 71 :3120-3128). HIV-1 strains tested is obtained from the NIH AIDS Reference and Reagent including 94US_3393 IN (catalog #11250), 90JJS873 (catalog #11251), 96TH NP1538 (catalog #11252), OOTZ_A246 (catalog #11256). In brief, Tl cells transduced with human CCRS are infected at a multiplicity of 0.1 tissue culture infectious doses per cell, and co-cultured in a 96-well plate with HIV1 CAR-transduced cells at a ratio of 5×10 4  to 1.25×10 4  cells respectively in 200 μl of R1 0-50, or no effector cells as a control. The effector cells are confirmed to be &gt;90% transduced. Each condition is run in triplicate, and viral replication is monitored using p24 quantitative ELISA (XpressBio, Frederick, MD). Exposure to HIV1 CAR cells is shown to lead to suppression of HIV1 as measured by p24 ELISA. 
     Effector cells expressing HIV1-CAR are also tested for antiviral activity against infected CD4+ cells. T2-CCRS cells are infected with a panel of HIV-1 strains including primary RS-tropic isolates and cultured in the absence or presence of the HIV1-CAR transduced effector cells. Virus replication is assessed by measurement of p24 antigen between days 7 to 10 of culture. Suppression of replication is calculated as the difference of logio units of p24 between cultures without versus with effector cells, which is then normalized as the ratio to total replication without effector cells. 
     Chromium Release Killing Assays for CAR-Mediated Killing of HIV-1-Infected Target Cells 
     T2-GLuc cells infected with HIV-1 strain NL4-3 as above are used as target cells for the HIV1-CAR transduced primary CD8+ T lymphocytes in Matador Assay or using standard  51 Cr-release assays as previously described (Bennett, et al. (2007) J Virol 81 :4973-4980; Yang, et al. (1996) J Virol 70:5799-5806; and Bennett, et al. (2010) Aids 24:2619-2628). Briefly, infected and control uninfected T2 cells are 51Cr-labeled for 1 hour and incubated with or without effector CD8+ T lymphocytes for 4 hours at varying cell ratios in a 96-well U-bottom plate. Supernatants are then harvested for measurement of extracellular 51Cr by micro204-scintillation counting in 96 well plates. Spontaneous release is measured on target cells without effector cells, and maximal release is measured on target cells lysed with 2.5% Triton X-100. Specific lysis is calculated as: (experimental released chromium-spontaneous release)÷(maximal release−spontaneous release). 
     Bispecific Antibodies Targeting MPL 
     Bispecific antibodies such as Bispecific T cell Engagers (BiTE) and Dual affinity retargeting (DART) can be used to retarget T cells to a target cell expressing a particular antigen. 
     A bispecific T cell engager based targeting MPL based on 161 scFV as the antigen binding domain is constructed. The sequence of this bispecific construct is shown in SEQ ID NO: 3736. The bispecific constructs contain a GGGSG-Streptagx2-Tag linker (SEQ ID NO: 287) but alternate linkers (e.g. SGGGS) can be used. 
     The bispecific construct was transfected in 293FT cells and supernatant containing the fusion protein collected after 48-96 hours. HEL-GLuc cells cultured with T cells in the presence of the MPL-161 bispecific fusion protein were shown to undergo cell lysis as determined by the GLuc assay as compared to the cells cultured with the bispecific fusion protein alone or T cells alone. 
     Bispecific antibodies encoding constructs based on 175, 111, hu-161-2, hu-175-2 and hu-111 scFv are next constructed and found to have activity in the HEL-GLuc cytotoxicity assay. Finally, bispecific antibodies targeting a number of other antigens, including PTK7, DLL3, TROP2, CD179a, CD179b, CD23, LAMP1, CDH1, CDH17, CD32, CDH19, HIV1-gp120 envelop glycoprotein etc., are similarly constructed and are found to have activity when co-cultured with the target cell lines expressing their cognate antigen. 
       FIG.  4   . Activity of a Bispecific T cell engager targeting MPL and using a 161-scFv targeting domain. HEL-pLenti-hGluc and T cells were pre-incubated separately with the following supernatants at 4° C. for 2h Medium alone and pLenti-161-Streptagll-CD3-Myc-His-P02 (042517-P02-SC). Post-incubation, cells were co-cultured in U-bottom 96-well plate at an E:T ratio of 1:1 or 5:1 for 4h at 37 C. 50 μl of cells+sup/well were transferred to 384 well plate in triplicate. hGLuc assay was performed using 15 ul of CTZ assay buffer (1:100). 
     Expression and activity of TFPs in Jurkat cells lacking TCRα and TCRβ expression. 
     Jurkat-NFAT-GFP (J-N-G) cells (T cell lymphoma) are infected with lentiviral vectors expressing gRNAs targeting TCRα and TCRβ1/02 constant chains and coexpressing Streptococcus Pyogenes Cas9. The exemplary gRNA target sequences for TCRα chains are given in SEQ ID NO: 7754 and 7755. The exemplary gRNA target sequences for TCRβ1/02 chains are given in SEQ ID NO: 7756-7758. In an alternatiave embodiment, the TCRα and TCRβ1/02 constant chain loci are targeting using gRNA and TALONs as described in Knipping F et al, Molecular Therapy: Methods &amp; Clinical Development, Vol 4, 2017. J-N-G cells lacking the expression of TCRα or TCRβ1/β2 chains are purified by cell sorting using antibodies directed against TCR/CD3 complex. Lentiviral vectors expressing TFPs directed against human MPL (SEQ ID NO: 2184, 2490, 2796) under EF1α promoter are used to infect parental J-N-G cells (control) and those lacking the expression of TCRα or TCRβ1/02 chains. Expression of TFPs in the cells is determined by immunostaining with Protein L staining and by staining with MPL-ECD-GGSG-NLuc-AcVS fusion protein (SEQ ID NO: 4923). J-N-G parental cells show robust TFP expression on cell surface while J-N-G cells lacking TCRα or TCRβ1/02 chains show poor to absent TFP expression. The different populations of J-N-G cells are exposed to HEL.92.1.7 target cells for 24 hours and examined for increase in NFAT-promoter driven GFP expression and IL2 production. J-N-G parental cells expressing MPL-specific TFPs show marked increase in GFP fluorescence and IL2 secretion upon co-culture with HEL.92.1.7 cells. In contrast, MPL-specific TFP-expressing J-N-G cells with absent TCRα or TCRβ1/02 chains show weak to no GFP induction and IL2 secretion. Essentially similar results are obtained when the experiment is repeated with J-N-G parental and TCRα- or TCRβ1/β2-deficient cells upon expression of TFPs targeting CD19 (SEQ ID NO: 1913, 2219, 2525), CD20 (SEQ ID NO: 1945, 2251, 2557) and CD22 (SEQ ID NO: 1950, 2256, 2562) and upon coculture with RAJI and Nalm6 target cells. 
     Next lentiviral vectors expressing codon optimized TCRα constant chain (IgSP-[hTRAC-opt2]; SEQ ID NO: 1010) or TCRβ constant chain (IgSP-[hTRBC-opt2]; SEQ ID NO: 1011) under EF1α promoter are used to infect the different J-N-G cell populations. Expression of TCRα constant chain in MPL-specific TFP-expressing J-N-G cells in which the TCRα chain has been disrupted by gRNA mediated gene knock out results in increased expression of TFP on the cell surface and induction of GFP expression and IL2 secretion upon co-culture with HEL.92.1.7 target cells. Similarly, expression of TCRβ constant chain in MPL-specific TFP-expressing J-N-G cells in which the TCRβ1/02 chain has been disrupted by gRNA-mediated gene knock out results in increased expression of TFP on the cell surface and induction of GFP expression and IL2 secretion upon co-culture with HEL.92.1.7 target cells 
     Expression and Activity of Ab-TCR and cTCR/SIRs in Jurkat Cells Lacking TCRα and TCRβ expression. 
     The above experiment is repeated with the exception that expression cassettes encoding Ab-TCRs and SIRs targeting human CD19 are used in place of TFPs targeting CD19. The Ab-TCRs targeting CD19 is represented by SEQ ID NO: 3124. The cTCR/SIRs targeting CD19 are represented by SEQ ID NO: 3878-3880. Expression of Ab-TCR, cTCR and SIR in J-N-G cells lacking TCRα or TCRβ1/02 expression is shown to results in increased expression and activity as compared to their expression in parental J-N-G cells. 
     Allogeneic and off-the-shelf T cells expressing CAR, TFP and Ab-TCR of the disclosure 
     Allogeneic or off-the-shelf CAR-T cells are generated by decreasing or eliminating the expression of endogenous TCRα and/or TCRβ chain using TALON, CRISP/Cas9 or other nucleases. 
     The MPL-specific TFP cassettes (SEQ ID Nos: 3527, 3529, 3531) are cloned in targeting constructs designed for targeting into the TRAC genomic locus and containing the right and left homology arms derived from TRAC genomic sequences. A polyadenylation sequence is inserted downstream of the stop codon of the TFPs. The schematic of the targeting construct and the targeting strategy is shown in  FIG.  5 A . The sequences of the targeting constructs are provided in SEQ ID NO: 3858, 7773 and 7776. The targeting constructs are cloned in an integration defective lentiviral vector (IDLV) and an Adeno-Associated Viral (AAV) vector. The constructs are directed to the TRAC locus in purified human T cells using CRISP/Cas9 ( FIG.  5 A ) as described in techniques known in the art and using the TRAC gRNA sequence (SEQ ID NO: 7751): 5′C*A*G*GGUUCUGGAUAUCUGUGUUUUAGAGCUAGAAAUAGCAAGUUAAAAU AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCU* U* U* U-3′. Asterisk (*) represents 2′ -0-methyl 3′ phosphorothioate. Exemplary techniques to deliver targeting constructs to the TRAC locus using IDLV and AAV are described in Knipping F et al, Molecular Therapy: Methods &amp; Clinical Development, Vol 4, 2017 and Eyquem J et al Nature, 543(7643):113-117, 2017, respectively. In parallel, purified human T cells are also transduced using the conventional approach with lentiviral vectors encoding the corresponding TFP constructs (SEQ ID NO: 2184, 2490, 2796) under EF1a promoter to generate cells expressing the different TFPs. Expression of TCRαβ and TFPs in the T cells is determined by immunostaining with TCR/CD3 antibodies and Protein L staining, respectively. Expression of TFPs on T cells is also examined by staining with MPL-ECD-GGSG-NLuc-AcV5 fusion protein (SEQ ID NO: 4923). The different populations of T cells are exposed to HEL.92.1.7-GLuc target cells and are compared using in vitro and in vivo assays of cell activation, proliferation, cytokine production (e.g., IL2), target cell lysis, senescence, exhaustion, in vivo expansion, in vivo persistence and in vivo anti-tumor activity. TFPs show impaired expression on T cells surface and reduced or absent activity (e.g., T cell activation, proliferation, cytokine production and cytotoxicity etc.) in T cell when their expression is directed to the TRAC locus as compared to when they are expressed using lentiviral vectors. It is next tested if expression of TCRα constant chain (TRAC chain) can be used to restore TFP expression and signaling and activity in T cells in which the endogenous TRAC genomic locus has been disrupted by the TFP expression cassette. For this purpose, targeting constructs are constructed that coexpress TFPs with an accessory module encoding a TCRα constant chain with an amino terminal signal peptide (IgSP) ( FIG.  5 B ). The accessory module is separated from the TFP encoding sequence by a Furine-SGSG-P2A linker. The nucleotide sequence of exemplary targeting constructs coexpressing a TCRα constant chain with TFP constructs targeting MPL are shown in SEQ ID NOs: 3859, 7774, and 7777). The nucleotide sequence of the TCRα constant chain in these constructs is codon optimized and differs from the endogenous TCRα constant chain in its nucleotide sequence. In an alternate embodiment, the TRAC chain is codon optimized and carries amino acid substitutions that are known to enhance the expression of human TCRα constant chain. The nucleotide sequence of exemplary exogenous TRAC chains that can be used to allow re-expression of TCR/CD3 complex in T cells in which the expression of endogenous TCRα gene has been down-regulated or eliminated by targeting are shown in SEQ ID NO: 3886 to 3894. The exogenous TRAC can be expressed in T cells either by itself (SEQ ID NO: 1010) or it can be co-expressed with the TFP expression cassettes using a single vector. 
     The MPL-specific TFP constructs (SEQ ID Nos: 3858, 7773 and 7776) and TFP-TRAC constructs (SEQ ID NOs: 3859, 7774, and 7777) are cloned in the IDLV and AAV vector and are directed to the TRAC locus essentially as described previously. 
     The cells expressing the constructs are exposed to HEL.92.1.7-GLuc target cells and tested in functional assays as described above. T cells in which the TFP-TRAC constructs are directed to the TRAC locus show better expression of TFP on cell surface as compared to T cells in which the TFP constructs alone (i.e. without coexpression of the exogenous TRAC chain) are directed to the TRAC locus. In addition, T cells in which the TFP-TRAC constructs are directed to the TRAC locus show greater proliferation, activation, cytokine (e.g., IL2 and TNFa) production, cytotoxicity, in vivo expansion, in vivo anti-tumor activity against the target cells as compared to T cells in which the TFP constructs alone (i.e. without coexpression of the exogenous TRAC chain) are directed to the TRAC locus. 
     The expression and activity of TFPs is also restored in T cells in which the endogenous TRAC locus has been disrupted by designing the targeting cassette such that TFP cassette is followed in frame by a 2A cleavable linker, a signal peptide (e.g., a CD8 signal peptide or an IgH signal peptide) and the first exon of the TCRα chain (TRAC) ( FIG.  5 C ). The nucleotide sequence of exemplary targeting constructs is shown in SEQ ID NO: 3860, 7775 and 7778. In this embodiment, the TRAC protein is produced by the endogenous TRAC chain whose cell surface expression is facilitated by the signal peptide provided in the targeting cassette. 
     The alloreactivity of the TFP-TRAC-expressing T cells which lack the expression of native TCRα chain but in which the TFP cell surface expression and activity is rescued by the expression of TCRα constant chain is tested using mixed lymphocyte culture reaction using irradiated T cells derived from an allogeneic donor. TFP-TRAC-expressing T cells which lack the expression of native TCRα show markedly reduced to absence of alloreactivity as measured by proliferative response as compared to T cells in which TFPs are expressed using lentiviral vectors. The ability of TFP-TRAC-expressing human T cells which lack the expression of native TCRα to induce Graft vs Host Disease (GVHD) is examined by administration of 5 million TFP-TRAC-expressing TCRa-deficient T cells per animal into immunodeficient NSG mice (Jackson Lab). Animals are observed for over 90 days. Human T cells in which the TFP-TRAC-cassettes are directed to the TRAC locus show markedly reduced to absence of Graft vs Host Disease (GVHD) when infused into immunodeficient NSG mice (Jackson Lab) while GVHD is observed in animals given T cells in which TFP are expressed using lentiviral vectors. The ability of TFP-TRAC-expressing TCRa-deficient T human T cells to induce Graft vs Host Disease (GVHD) is also examined by administration of 1 million cells per kilogram into allogeneic human recipients who have received lymphodepleting chemotherapy. Allogeneic T cells in which the TFP-TRAC cassettes are directed to the TRAC locus show markedly reduced incidence and severity of Graft vs Host Disease (GVHD) when given to allogeneic recipients. 
     Essentially similar results are obtained when the experiment is repeated with T cells in which the TFPs are directed to the TRBC locus. The target sequence of gRNA targeting TRBC are shown in SEQ ID NO: 7756-7758. These gRNAs are used in combination with Streptococcuc Pyogenes Cas9 using methods known in the art. Directing the TFP expression cassettes to the TRBC genomic locus is shown to result in impaired activity of the MPL-specific TFPs. However, the activity of TFPs is restored by coexpression of exogenous TCRβ constant chain (TRBC). The nucleotide sequence of exemplary exogenous TRBC chains that can be used to restore TCR/CD3 complex signaling function are shown in SEQ ID NO: 3899-3910. The exogenous TRBC can be expressed in T cells either by itself (SEQ ID NO: 1011) or it can be co-expressed with the TFP expression cassettes from a single vector. The nucleotide sequence of exemplary constructs coexpressing a TRBC chain with TFP constructs targeting MPL are shown in SEQ ID NO: 3537, 3539 and 3541. These TFP expression constructs can be cloned in suitable TRBC targeting vectors using techniques known in the art. In an alternate embodiment, the expression of TRBC can be restored in T cells in which the endogenous TRBC locus has been disrupted by designing the targeting cassette such that TFP cassette is followed in frame by a 2A cleavable linker, a signal peptide (e.g., a CD8 signal peptide or an IgH signal peptide) and the first exon of the TCRβ chain (TRBC). 
     Directing the Ab-TCR Constructs to the TRAC Locus 
     Two Ab-TCR constructs targeting CD19 based on FMC63 scFv are generated in lentiviral vector (SEQ ID NO: 3837) driven by EF1α promoter. The nucleotide sequences of these constructs, CD8SP-FMC63-vL-RgCL-TCRb-IAH-6MD1-F-P2A-SP-FMC63-vH-[IgG1-CH1-TCRa-SDVP-6MD] and CD8SP-FMC63-vL-KgCL-TCRg-6MD1-F-P2A-SP-FMC63-vH4-[IgG1-CH1-TCRd-6MD] are represented by the nucleotide sequences encoding the Ab-TCR component of SEQ ID NO: 3124 and 3324. Primary human T cells are infected with the corresponding lentiviral supernatants and assayed for the cell surface expression of the Ab-TCRs using FLAG-CD19-ECD-GGSG-NLuc-AcV5 supernatant (SEQ ID NO: 1014) and for cytotoxicity against RAJI-GLuc cells. T cells expressing the Ab-TCRs show modest expression and activity. The expresson of the Ab-TCRs is directed to the TRAC locus essentially as described by Eyquem J et al (Nature, 543(7643):113-117, 2017) using gene targeting constructs (see,  FIG.  6   ) and represented by SEQ ID NO: 3861-3864. The targeting construct contains a splice acceptor (SA), followed by a F2A coding sequence, the Ab-TCR cassette, flanked by sequences homologous to the TRAC locus (LHA and RHA, left and right homology arm). In cassettes A and B (SEQ ID NO: 3861-3862), the nucleotide sequence coding the Ab-TCR expression cassettes are followed by a stop codon, polyA sequences, Exon 1 of TRAC and the sequence homologous to the TRAC locus (RHA: right homology arm). In cassette C, nucleotide sequence coding the Ab-TCR expression cassette is followed by a stop codon, Exon 1 of TRAC and the sequence homologous to the TRAC locus (RHA: right homology arm) but without a poly A sequence so that the transcript carries at its 3′ end the TRAC gene and its polyadenylation sequence. In cassette D, the Ab-TCR cassette lacks its own TCRα module and extends only upto the IgG1-CH1 region, which is fused in frame to 3′ half of the first exon of TRAC. Thus, in this construct, the TCRα module is encoded by the genomic TRAC locus containing part of exon 1, and whole of exon 2 and exon 3. Cassette E resembles cassette D except that the RHA in the targeting construct carries mutations (SDVP) that can enhance the expression of TRAC. T cells in which the Ab-TCR cassettes are directed to the TRAC locus uniform and physiological expresson and long-term persistence and activity of the transgene as determined using in vivo and in vitro assays as compared to Ab-TCR cassettes expressed using lentiviral vectors. The Ab-TCR expressing T cells are purified by staining with PE-Protein L followed by flow sorting. The alloreactivity of the Ab-TCR-expressing T cells is tested using mixed lymphocyte culture reaction using irradiated T cells derived from an allogeneic donor. T cells in which the Ab-TCRs are directed to the TRAC locus show markedly reduced to absence of alloreactivity as measured by proliferative response as compared to T cells in which Ab-TCRs are expressed using lentiviral vectors. The ability of Ab-TCR expressing human T cells to induce Graft vs Host Disease (GVHD) is examined by administration of 5 million Ab-TCR expressing T cells per animal into immunodeficient NSG mice (Jackson Lab). Animals are observed for over 90 days. Human T cells in which the Ab-TCR cassettes are directed to the TRAC locus show markedly reduced to absence of Graft vs Host Disease (GVHD) when infused into immunodeficient NSG mice (Jackson Lab) while GVHD is observed in animals given T cells in which Ab-TCRs are expressed using lentiviral vectors. The ability of Ab-TCR expressing human T cells to induce Graft vs Host Disease (GVHD) is also examined by administration of Ab-TCR expressing T cells (1 million cells per kilogram) into allogeneic human recipients. Allogeneic T cells in which the Ab-TCR cassettes are directed to the TRAC locus show markedly reduced incidence and severity of Graft vs Host Disease (GVHD) when given to allogeneic recipients. Essentially similar results are obtained using T cells in which Ab-TCR are expressed by directing the expression cassettes to the TRBC locus. 
     Directing the chimeric TCR or Synthetic Immune Receptors (SIR) constructs to the TRAC locus 
     Three cTCRs (or SIR) constructs targeting CD19 based on FMC63 scFv are generated in lentiviral vector (SEQ ID NO: 3837) driven by EF1α promoter. The nucleotide sequences of these constructs are represented by SEQ ID NO: 3878, 3879 and 3880, respectively. They all have the same vL and vH regions. While the SEQ ID NO: 3880 has the wild-type nucleotide sequence of TCRα and TCRβ constant chains, the SEQ ID NO: 3878 and 3879 have codon opitimized sequences. The SEQ ID NO: 3878 further carries several amino acid substitutions to enhance the expression and base-pairing of the TCRα and TCRβ constant chains. Primary human T cells are infected with the corresponding lentiviral supernatants and assayed for the cell surface expression of the SIR using FLAG-CD19-ECD-GGSG-NLuc-AcV5 supernatant (SEQ ID NO: 1014) and for cytotoxicity against RAJI-GLuc cells. The cTCR/SIR construct with SEQ ID NO: 3880 is not found to express well or to induce target cell lysis. The cTCR/SIR are also directed to the TRAC locus essentially as described by Eyquem J et al (Nature, 543(7643):113-117, 2017) using exemplary gene targeting constructs (see,  FIG.  7   ) represented by SEQ ID NO: 3865 to 3868, and 3873. The targeting construct contains a splice acceptor (SA), followed by a F2A coding sequence, the Ab-TCR cassette, flanked by sequences homologous to the TRAC locus (LHA and RHA, left and right homology arm). In cassettes A and B (SEQ ID NO: 3865, 3866 and 3873), the nucleotide sequence coding the SIR expression cassettes are followed by a stop codon, polyA sequences, Exon 1 of TRAC and the sequence homologous to the TRAC locus (RHA: right homology arm). In cassette E, nucleotide sequence coding the SIR expression cassette is followed by a stop codon, Exon 1 of TRAC and the sequence homologous to the TRAC locus (RHA: right homology arm) but without an intervening poly A sequence so that the transcript carries at its 3′ end the TRAC gene and its polyadenylation sequence. In cassette D, the SIR cassette lacks its own TCRα module and extends only upto the FMC63-vH region, which is fused in frame to the first exon of TRAC present in the targeting construct. Thus, in this construct, the TCRα module is encoded by the genomic TRAC locus containing part of exon 1, and whole of exons 2 and 3. Cassette F resembles cassette E except that the RHA in the targeting construct carries mutations (CSDVP) in the exons 1 and 2 of TRAC that can enhance the expression of TRAC. T cells in which the cTCR/SIR cassettes are directed to the TRAC locus (SEQ ID NO: 3873) show uniform and physiological expresson and long-term persistence and activity of the transgene as determined using in vivo and in vitro assays as compared to cTCR/SIR cassettes expressed using lentiviral vectors. Other cTCRs (SEQ ID NO: 3865-3868) also show uniform expression and activity when directed to the TRAC locus. The cTCR and SIR expressing T cells are purified by staining with FITC conjugated CD3 antibody and PE-Protein L followed by flow sorting. The alloreactivity of the cTCR-and SIR-expressing T cells is tested using mixed lymphocyte culture reaction using irradiated T cells derived from an allogeneic donor. T cells in which the cTCR/SIR are directed to the TRAC locus show markedly reduced to absence of alloreactivity as measured by proliferative response as compared to T cells in which cTCR/SIR are expressed using lentiviral vectors. The ability of cTCR/SIR expressing human T cells to induce Graft vs Host Disease (GVHD) is examined by administration of 5 million cTCR/SIR expressing T cells per animal into immunodeficient NSG mice (Jackson Lab). Animals are observed for over 90 days. Human T cells in which the cTCR/SIR cassettes are directed to the TRAC locus show markedly reduced to absence of Graft vs Host Disease (GVHD) when infused into immunodeficient NSG mice (Jackson Lab) while GVHD is observed in animals given T cells in which cTCR/SIR are expressed using lentiviral vectors. The ability of cTCR and SIR expressing human T cells to induce Graft vs Host Disease (GVHD) is also examined by administration of cTCR/SIR expressing T cells (1 million cells per kilogram) into allogeneic human recipients who have received lymphodepleting chemotherapy. Allogeneic T cells in which the cTCR/SIR cassettes are directed to the TRAC locus show markedly reduced incidence and severity of Graft vs Host Disease (GVHD) when given to allogeneic recipients. Essentially similar results are obtained using T cells in which cTCR and SIR are expressed by directing the expression cassettes to the TRBC locus. 
     Directing a TCR or a cTCR/SIR Constructs to the TRAC Locus 
     A TCR construct and a cTCRs (or SIR) construct targeting NY-ESO-1/HLA-A2 complex are generated in lentiviral vector (SEQ ID NO: 3837) and are based on TCR NYESO-1G4 and TCR mimic antibody NYESO-35-15. The nucleotide sequences of these constructs are represented by SEQ ID NO: 3883 and 3882, respectively. The two constructs are also targeted to the TRAC locus using the targeting constructs represented by SEQ ID NO: 3874-3877. The design of the targeting construct is shown in  FIG.  8   . T cells in which the NY-ESO-1 TCR or cTCR is directed to the TRAC locus show uniform expression of the transgene, good recognition of target cells expressing NY-ESO-1/HLA-A2 complex and perform equally well or better than T cells in which the above constructs are expressed using lentiviral mediated gene transfer using in vivo assays. Human T cells in which the NY-ESO-1 TCR or cTCR is directed to the TRAC locus also show reduced alloreactivity in mixed lymphocyte reacton and reduced GVHD in NSG mice xenograft model as compared to the T cells in which the the NY-ESO-1 or cTCR are expressed using lentiviral mediated gene transfer. 
     Directing a single chain cTCR/SIR Construct to the TRAC Locus 
     Single chan cTCR/SIRs in which FMC63-scFv is attached to codon optimized TCRα constant chain or codon optimized plus murinized TCRα constant chain (SEQ ID NO: 3881) are expressed in T cells using lentiviral vector and show poor expression and activity. The same constructs are directed to the TRAC locus using the targeting constructs shown in  FIG.  9    and represented by SEQ ID NO: 3869-3872. T cells in which the single chain cTCRs/SIRs are directed to the the TRAC locus show uniform expression and activity of the cTCR when assayed using the assays described previously. In addition, T cells in which the single chain cTCR/SIR are directed to the TRAC lcous show reduced incidence of alloreactivity using MLR and reduced incidence of GVHD using NSG mice xenograft model as compared to the T cells in which the the NY-ESO-1 or cTCR are expressed using lentiviral mediated gene transfer. 
     In the above examples, the CAR/TFP/Ab-TCR/TCR/cTCRs are directed to the TRAC locus. Essentially a similar procedure can be used to direct the CAR/TFP/Ab-TCR/TCR/cTCR or an accessory module to the TCBC, CD3ε, CD3δ, CD3γ, and CD3ζ loci using techniques known in the art. 
     A shorter EF1α promoter retains strong promoter activity in T cells and is suitable for adoptive cellular therapy 
     Use of strong viral promoters in adoptive cellular therapy applications carries the risk of activation of downstream oncogenes and development of cancer. As such, human Elongation Factor la (EF1a) promoter is frequently used in adoptive cellular therapy applications as it provides strong expression and is human in origin. A limitation of EF1a promoter, however, is its relatively large size. Although a mini-EF1a promoter has been described, it is much weaker as compared to the EF1a promoter. To determine whether an internal deletion in the EF1a promoter would allow shortening of its length while preserving its promoter strength, a SacII fragment was deleted from the EF1α promoter. The nucleotide sequence of the resulting EF1a-D-SacII promoter is presented in SEQ ID NO: 3842. Lentiviral vectors encoding a CD19-directed FMC63-BBz CAR were constructed in the vectors with the wild-type EF1α promoter (SEQ ID NO: 3840) or EF1a-D-SacII promoter (SEQ ID NO: 3839). The vectors also co-expressed EGFP and blasticidin resistance gene via 2A linkers. Lentiviruses were generated in 293FT cells and used to infect J-N-G cells. Infected cells were selected with blasticidin and then tested for their ability to induce EGFP expression upon co-culture with CD19+ve RAJI cells. Near equivalent inducton of EGFP expression was observed in J-N-G cells transduced with either lentiviral construct. In addition, near equivalent expression of the FMC63-BBz CAR was observed on the surface of J-N-G cells transduced with either construct as determined by binding with CD19-ECD-GGS-NLuc fusion protein. These results demonstrate that the EF1a-D-SacII promoter can be used for adoptive cellular therapy applications. The results further demonstrate that the EF1a-D-SacII promoter is not more prone to silencing than the the wild-type EF1α promoter and can be used for long-term transgene expression. 
     Use of water soluble Dasatinib Salt for control of Cytokine release syndrome and neurological complications obsereved during adoptive cellular therapy 
     Dasatinib is a poorly water soluble drug and commercial Dasatinib is a monohydrate and reported to have solubility of 8 μg/mL at 24° C. As patients with CRS and neurological complications have difficulty taking the oral form of Dasatinib, water soluble form of Dasatinib is desireable. Water soluble salts of Dasatinib have been described in W02015107545 Al. Injectable compositions comprising soluble salts of Dasatinib methane sulphonate monohydrate can be prepared according to the method of WO2015107545 A1 and used to treat patients with CRS and neurological complications associated with administration of CAR-T cells and Blinatumomab. The dose of Dasatinib methane sulphonate monohydrate can be titrated up to achieve an effective plasma concentration. In an exemplary embodiment, the plasma concentration of Dasatinib is kept higher than 10 nM, 20 nM, 50 nM, 100 nM, 200 nM or 300 nM. In another exemplary embodiment, the plasma concentration of Dasatinib is kept higher than 5 ng/ml, 15 ng/ml, 25 ng/ml, 50 ng/ml or 75 ng/ml. Finally, Dasatinib methane sulphonate monohydrate dissolved in normal saline can be also used for intra-thecal administration in patients with neurological complications from CAR-T cells and Blinatumomab. In an exemplary embodiment, the intra-thecal dose of Dasatinib methane sulphonate is adjusted to achieve CSF concentration higher than 10 nM, 20 nM, 50 nM, 100 nM, 200 nM or 300 nM. In an exemplary embodiment, the intra-thecal dose of Dasatinib methane sulphonate is adjusted to achieve CSF concentration higher than higher than 5 ng/ml, 15 ng/ml, 25 ng/ml, 50 ng/ml or 75 ng/ml. 
     Use of autologous T cells expressing conventional CARs and backbones 1-72 targeting multiple antigens for adoptive cell therapy 
     Patients with many different diseases, including infectious diseases (e.g., HIV1, EBB, CMV, HTLV1, etc), degenerative diseases (e.g., Alzheimer&#39;s disease), allergic diseases (e.g., chronic idiopathic urticarial) and multiple cancers will be enrolled in an IRB approved phase I clinical trial of immunotherapy with adoptively transferred autologous CAR-T cells coexpressing NEMO-K277A (backbone 2) targeting different disease-causing or disease-associated antigens. The CAR for different diseases will be selected based on the known expression of their target antigen in the disease-causing or disease-associated cells. Where possible, the expression of the CAR target on the disease causing or disease associated cells will be confirmed by binding with Antigen binding domain-GGS-NLuc fusion protein in which the antigen binding domain of the CAR is fused to non-secretory form of NLuc protein via a flexible linker. Alternatively, immunohistochemistry or flow cytometry using commercially available antibodies will be used to confirm the expression of the target antigen of the CAR on disease-causing or disease-associated cells. T cells will be collected from the subjects using leukopheresis, transduced with the appropriate lentivirus vectors and expanded ex vivo using CD3/CD28 beads in a closed system. After the resulting cell products have undergone quality control testing (including sterility and tumor specific cytotoxicity tests), they will be cryopreserved. CAR-T cell products will be administered to the subjects as described in the preceding example. Clinical and laboratory correlative follow-up studies can then be performed at the physician&#39;s discretion. Essentially a similar approach is used to test CARs in other backbones described in this disclosure. 
     Use of allogeneic T cells expressing conventional CARs and backbones 1-72 targeting multiple antigens for adoptive cell therapy 
     Patients with many different diseases, including infectious diseases (e.g., HIV1, EBB, CMV, HTLV1, etc), degenerative diseases (e.g., Alzheimer&#39;s disease), allergic diseases (e.g., chronic idiopathic urticarial) and multiple cancers will be enrolled in an IRB approved phase I clinical trial of immunotherapy with adoptively transferred allogenic CAR-T cells targeting different disease-causing or disease-associated antigens. The CAR for different diseases will be selected based on the known expression of their target antigen in the disease-causing or disease-associated cells. Where possible, the expression of the CAR target on the disease causing or disease associated cells will be confirmed by binding with Antigen binding domain-GGS-NLuc fusion protein in which the antigen binding domain of the CAR is fused to non-secretory form of NLuc protein via a flexible linker. Alternatively, immunohistochemistry or flow cytometry using commercially available antibodies will be used to confirm the expression of the target antigen of the CAR on disease-causing or disease-associated cells. T cells will be collected from a healthy donor using leukopheresis. The CAR expression cassette (SEQ ID NO: 1900 to SEQ ID NO: 2205) are cloned in the targeting vector and the CAR module is directed to the TRAC locus in the T cells essentially as described by (Eyquem J et al, Nature, 543(7643):113-117). T cells lacking CD3 expression on the surface are selected by immunomagnetic purification and then expanded ex vivo using CD3/CD28 beads in a closed system. After the resulting cell products have undergone quality control testing (including sterility and tumor specific cytotoxicity tests), they will be cryopreserved. CAR-T cell products will be administered to the subjects as described in the preceding example. Clinical and laboratory correlative follow-up studies can then be performed at the physician&#39;s discretion. Essentially a similar approach is used to test CARs in other backbones, including CARs that co-express TCRα constant chain (TRAC) lacking the Va domain, described in this disclosure. 
     CAR-T Cell Hepatic Arterial Infusion 
     In addition to intravenous infusion, T cells expressing the conventional CARs and backbones 1-72 described in this invention can be infused intra-arterially to provide high concentration of CAR-T cells in a local area or organ involved with a disease. In the following example, this approach is used in case of a patient with hepatic metastases from a gastrointestinal cancer which expresses Folate Receptor alpha (FR1). Essentially a similar approach can be used for intra-arterial infusion of T cells expressing conventional CARs and backbones 1-72 targeting other tumor antigens. 
     A mapping angiogram will be performed via a right common femoral artery approach at baseline. The gastroduodenal and right gastric arteries, in addition to other potential sources of extrahepatic perfusion, will be embolized with microcoils. The same arterial access procedure will be carried out for administration of T cells expressing the construct CD8SP-FR1-huMov19-(vL-vH)-Myc-z-P2A-hNEMO-K277A-T2A-PAC (SEQ ID NO: 1727). The T cells will be collected from the patient on day 0 and will be infected with lentivirus encoding the construct CD8SP-FR1-huMov19-(vL-vH)-Myc-z-P2A-hNEMO-K277A-T2A-PAC and expanded as described in the previous examples. The CAR-T cells will be given in a dose escalating fashion on day 14 (10 7  CAR-T cells), day 28 (10 8  CAR-T cells) and day 44 (10 9  CAR-T cells). The CAR-T cells will be injected manually via a 60cc syringe at a rate of &lt;2 cc/second. The total volume of infusion will be approximately 100 cc. Angiography with calibrated contrast rate will be performed after the first infusion of 50 cc and at completion of the CAR-T infusion to confirm preserved arterial flow. Infusions will be delivered into the proper hepatic artery when possible. Certain patients may have aberrant hepatic arterial anatomy, where either the right or left hepatic artery does not arise from the proper hepatic artery. In such cases the dose of CAR-T cells will be split based upon lobar volume calculations. In such cases, split doses will be delivered separately into the right and left hepatic arteries to ensure proportionate CAR-T delivery to both hepatic lobes. 
     Intraperitoneal administration of CAR-T cells 
     CAR-T cells can also be administered intraperitoneally, essentially as described in Koneru M et al (Journal of Translational Medicine; 2015; 13:102). In the following example, this approach is used in patients with peritoneal involvement with ovarian cancer which expresses Folate Receptor alpha (FR1). Essentially a similar approach can be used for intra-peritoneal infusion of CAR-T cells targeting other tumor antigens described in this disclosure. 
     A screening informed consent will be offered to patients with recurrent high-grade serous ovarian cancer to test their cancer for the expression of FR1. After expression of FR1 is confirmed by immunohistochemistry, then patients will have a leukapheresis product obtained from peripheral blood. Excess platelet and red blood cell contamination will be removed from the leukapheresis product and the product will be frozen. In the treatment phase of the study, the leukapheresis product will be thawed and washed. Subsequently, CD3+ T cells will be isolated from the thawed leukapheresis product by magnetic separation using CD3/CD28 beads. Activated T cells will be lentivirally transduced with the CD8SP-FR1-huMov19-(vL-vH)-Myc-z-P2A-hNEMO-K277A-T2A-PAC construct and further expanded using CD3/CD28 bead expansion protocol. 
     Patients with recurrent high-grade serous ovarian, primary peritoneal or fallopian tube carcinoma shown to express FR1 antigen confirmed by immunohistochemistry (IHC) analysis of banked (paraffin embedded) or freshly biopsied tumor will potentially be eligible for the study. 
     The phase I dose-escalation dosing will be used in the trial. Cohorts of 3-6 patients will be infused with escalating doses of modified T cells to establish the maximum tolerated dose (MTD). There will be four planned dose levels: 3×10 5 , 1×10 6 , 3×10 6 , and 1×10 7  CAR-T cells/kg. Cohorts I and II will be treated with 3×10 5  CAR-T cells/kg but patients in cohort II will also receive lymphodepleting cyclophosphamide. Cohorts II-V will receive escalating doses of the modified T cells following pretreatment with cyclophosphamide. Lymphodepleting cyclophosphamide dosed at 750 mg/m 2  will be administered 2-4 days prior to the initial T cell infusion. A standard 3+3 dose escalation schema will be followed. 
     An IP catheter will be placed prior to T cell infusion. Patients will be admitted to the inpatient unit of the hospital prior to their first infusion of CAR T cells and will remain hospitalized until at least 3 days after the second infusion of CAR T cells. The first cohort of patients to be treated, and the first patient treated in each subsequent cohort, will be admitted to the intensive care unit (ICU); subsequent patients may be admitted to the medical oncology inpatient service (subject to the clinical judgment of the treating physician). 
     Patients will receive a single dose of lymphodepleting cyclophosphamide (750 mg/m 2  IV) chemotherapy 2 to 4 days prior to initiating treatment with CAR-modified T cells. The transduced T cells will be quality tested for number, purity, viability, and sterility prior to infusion. All patients will receive 50% of the genetically modified T cell dose intravenously. Patients will be closely monitored for toxicities. One to 3 days later, the remaining dose of T cells will be administered as an IP infusion. At least 3 patients will be treated at dose level 1, with an accrual of no more than 2 patients per month within each dose level. All patients treated in the preceding cohort will be observed for a minimum of 4 weeks from the day of the initial T cell infusion before escalation to the next cohort occurs. Blood samples will be obtained from all patients prior to and following treatment to assess toxicity, therapeutic effects, and survival of the genetically modified T cells. 
     Use of CAR-T Cells for Intratumoral Injection 
     CAR-T cells can also be administered intra-tumorally, essentially as described in Brown CE, et al, Clin Cancer Res. 2015 September 15; 21(18): 4062-4072. In the following example, this approach will be used in case of patients with recurrent glioblastoma (GBM) which expresses IL13Ra2. Essentially a similar approach can be used for intra-tumoral injection of T cells expressing conventional CARs or conventional CARs expressing accessory modules (backbones 1-72) targeting other tumor antigens. 
     A pilot safety and feasibility study will be conducted to test CD8SP-IL13Ra2-Hu108-(vL-vH)-Myc-z-P2A-hNEMO-K277A-T2A-PAC (SEQ ID NO: 1769) expressing T cells in recurrent GBM. All participating patients will be required to give written informed consent. The clinical protocol will be approved by the University of Southern California Institutional Review Board and conducted under an Investigational New Drug Application, and registered at ClinicalTrials.gov. Eligible patients will include adults (18-70 yrs) with recurrent or refractory unifocal supratentorial grade III or IV glioma whose tumors do not show communication with ventricles/CSF pathways and are amenable to resection. Participation in this trial will be independent of IL13Ra2 (or IL13Ra2) tumor antigen status. Patients will be enrolled following initial diagnosis of high-grade glioma (WHO grade III or IV), at which time they will undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMC). These cells will be used to engineer T cells to express the construct CD8SP-IL13Ra2-Hu108-(vL-vH)-Myc-z-P2A-hNEMO-K277A-T2A-PAC containing the puromycin resistance gene (PAC) following infection with the corresponding lentiviral vector as described in the previous examples. Alternatively, the CAR-T cells could be generated following infection with a retroviral vector or using sleeping beauty transposon or by transfection of IVT mRNA. Subsequently, the release tested therapeutic CAR-T cells will be cryopreserved and stored for later use. At the time of first recurrence of the tumor, the research participant will undergo resection of tumor along with placement of a Rickham reservoir/catheter. Concurrently, the therapeutic CAR-T cells will be thawed, re-expanded in vitro using CD3/CD28 beads based rapid expansion protocol. Following recovery from surgery and post baseline MR imaging, the CAR-T cells will be administered directly into the resection cavity via the indwelling catheter, essentially as described (Brown CE, et al, Clin Cancer Res. 2015 21(18): 4062-4072). Cells will be manually injected into the Rickham reservoir using a 21 gauge butterfly needle to deliver a 2 mL volume over 5-10 minutes, followed by 2 mL flush with preservative free normal saline over 5 minutes. The protocol treatment plan will specify an intra-patient dose escalation schedule with a target of 12 CAR T cell doses administered intracranially over a 5 week period comprised of weekly treatment cycles. During cycles 1, 2, 4 and 5, T cell infusions will be performed on days 1, 3 and 5 of the cycle week, and week 3 will be a rest cycle. For safety, in cycle 1 an intrapatient dose escalation strategy, with CART cell doses of 10 7 , 5×10 7  and 10 8  cells per infusion administered on days 1, 3 and 5 respectively, will be used and this will be followed by 9 additional CART cell infusions of 10 8  cells over 4 weeks. Imaging to assess response will be performed during the week 3 rest cycle and after week 5. The guidelines provided in the NCI Common Toxicity Criteria version 2.0 (https://ctep.ifo.nih.gov/1) will be followed for the monitoring of toxicity and adverse event reporting. 
     Use of CAR-T cells for ex-vivo purging of bone marrow or peripheral blood stem cell preparation prior to transplant 
     CART cells can be used to purge the bone marrow or peripheral blood stem cell preparation of cancer cells prior to stem cell transplant. In the following example, CD8SP-CS1-HuLuc64-(vL-vH)-Myc-z-P2A-hNEMO-K277A-T2A-PAC (SEQ ID NO: 1699) expressing T cells will be used to purge bone marrow or peripheral blood stem cells obtained from a patient with multiple myeloma prior to autologous stem cell (or bone marrow) transplant. 
     Patient will undergo leukopheresis to collect peripheral blood mononuclear cells (PBMC). T cells will be purified using CD3 beads. These cells will be used to engineer T cells to express the CD8SP-CS1-HuLuc64-(vL-vH)-Myc-z-P2A-hNEMO-K277A-T2A-PAC CAR following infection with the corresponding lentiviral vector as described in the previous examples. Subsequently, the release-tested therapeutic CAR-T cells will be cryopreserved and stored for later use or used fresh. Bone marrow cells and peripheral blood progenitor cell products will be collected from a patient with multiple myeloma following standard procedures. For mobilization of peripheral blood stem cells, patients will receive cyclophosphamide, 3 gm/m 2  followed by G-CSF, 10 μg/kg subcutaneously each day beginning 24 h after cyclophosphamide until pheresis is complete. Peripheral blood stem cells will be collected once the peripheral blood CD34+-cell count is 15 cells/pl. The collection goal will be to process three blood volumes per day until a minimum of 2.0 times 10 6  CD34+ cells/kg are reached after processing. The bone marrow and peripheral blood stem cell products will be optionally depleted of Red Blood Cells and/or enriched for CD34 expressing cells using CliniMACS Prodigy® System from Miltenyi Biotec and following the manufacturer&#39;s recommendations. The products will be used for ex-vivo purging fresh or cryopreserved. For purging, the bone marrow or peripheral blood stem cell products will be cocultured with thawed CAR-T cells at an effector to target ratio ranging from 5: 1 to 30:1 for 4 to 24 hours in XVIVO medium (Lonza) supplanted with 100 IU recombinant human-IL2. Cells will be cultured at 37° C., in a 5% CO2 humidified incubator. At the end of the coculture period, an aliquot of the cells will be taken for sterility and quality testing (including measurement of CFU-GM and flow cytometry for CD34 and CD138 positive cells). The remaining sample will be administered intravenously to the patient who has previously received myeloablative chemotherapy (e.g., high dose Melphalan in two divided doses of 70 mg/m 2  for a total dose of 140 mg/m 2 ). 
     Use of Bispecific T Cell Engagers 
     Proteins encoded by the Bispecific T cell engagers are expressed in Hela cells using the constructs having the SEQ ID Nos listed in Table 13. The proteins are purified using Metal affinity tag or StrepTag II columns using standard protein purification techniques. The purified proteins are tested in phase I clinical trials. Patients are selected based on the expression of the target antigens of the bispecific antibodies using different assays known in the art. The bispecific antibodies are administered by 24 hour infusion. The guidelines provided in the NCI Common Toxicity Criteria version 2.0 (http[s://]ctep.ifo.nih.gov/1) are followed for the monitoring of toxicity and adverse event reporting. 
     Use of CAR Combinations 
     Patients with mesothelioma and glioblastomas are administered T cells infected with lentiviruses encoding the following combination of CARs targeting Mesothelin (expressed on mesotheloma), IL13Ra2 (expressed on Glioblastomas) and hematopoietic markers (CD19, CD20, CD22, BCMass.). The T cells are either of the wild-type TCR chains or have the TCRα chain knocked out by CRISP/Cas9 approach. It is observed that coexpression in the same T cells with the wild-type TCR chains of a CAR targeting mesothelin with a CAR targeting CD19, CD20, CD22 or BCMA results in increased T cell expansion in vivo as compared to expression of Mesothelin alone. Essentially similar results are obtained with CAR targeting glioblastoma. However, in T cells that are defective in TCR chains, coexpression of TFP based CARs targeting CD20 (SEQ ID NO: 9660) fail to induce in vivo expansion while co-expression of SIR (SEQ ID NO: 9668) or Ab-TCR (SEQ ID NO: 9676) based CARs succesfully induces T cells expansion. 
     
       
         
           
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                 Effect of CAR combination on in vivo T cell expansion 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 Target 
                 SEQ 
                 Target 
                 SEQ 
                   
               
               
                   
                   
                 antigen 
                 ID of 
                 antigen 
                 ID of 
               
               
                   
                 T cells TCR 
                 of 1st 
                 1st 
                 of 2nd 
                 2nd 
                 Tcell 
               
               
                 Disease 
                 status 
                 CAR 
                 CAR 
                 CAR 
                 CAR 
                 Expansion 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Mesothelioma 
                 Wild Type 
                 Mesothelin 
                 1505 
                 None 
                   
                 Poor 
               
               
                 Mesothelioma 
                 Wild Type 
                 Mesothelin 
                 1505 
                 CD19 
                 1016 
                 Good 
               
               
                 Mesothelioma 
                 Wild Type 
                 Mesothelin 
                 1505 
                 CD19 
                 1607 
                 Good 
               
               
                 Mesothelioma 
                 Wild Type 
                 Mesothelin 
                 1505 
                 CD20 
                 1631 
                 Good 
               
               
                 Mesothelioma 
                 Wild Type 
                 Mesothelin 
                 1505 
                 CD22 
                 1644 
                 Good 
               
               
                 Mesothelima 
                 Wild Type 
                 Mesothelin 
                 1505 
                 BCMA 
                 1624 
                 Good 
               
               
                 Glioblastoma 
                 Wild Type 
                 IL13Ra2 
                 1493 
                 None 
                   
                 Poor 
               
               
                 Glioblastoma 
                 Wild Type 
                 IL13Ra2 
                 1493 
                 CD19 
                 1016 
                 Good 
               
               
                 Glioblastoma 
                 Wild Type 
                 IL13Ra2 
                 2075 
                 CD19 
                 1607 
                 Good 
               
               
                 Glioblastoma 
                 Wild Type 
                 IL13Ra2 
                 2381 
                 CD20 
                 1631 
                 Good 
               
               
                 Glioblastoma 
                 Wild Type 
                 IL13Ra2 
                 2687 
                 CD22 
                 1644 
                 Good 
               
               
                 Glioblastoma 
                 Wild Type 
                 IL13Ra2 
                 2687 
                 BCMA 
                 1624 
                 Good 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 2075 
                 CD20 
                 9660 
                 Poor 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 2381 
                 CD20 
                 9660 
                 Poor 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 2687 
                 CD20 
                 9660 
                 Poor 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 1493 
                 NOne 
                   
                 Poor 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 1493 
                 CD20 
                 9668 
                 Good 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 2075 
                 CD20 
                 9676 
                 Good 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 2381 
                 CD20 
                 9668 
                 Good 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 2687 
                 BCMA 
                 9362 
                 Good 
               
               
                 Glioblastoma 
                 TCR-alpha-ve 
                 IL13Ra2 
                 2687 
                 BCMA 
                 9362 
                 Good 
               
               
                   
               
            
           
         
       
     
     The various methods and techniques described above provide a number of ways to carry out the application. Of course, it is to be understood that not necessarily all objectives or advantages described can be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the methods can be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as taught or suggested herein. A variety of alternatives are mentioned herein. It is to be understood that some preferred embodiments specifically include one, another, or several features, while others specifically exclude one, another, or several features, while still others mitigate a particular feature by inclusion of one, another, or several advantageous features. 
     Furthermore, the skilled artisan will recognize the applicability of various features from different embodiments. Similarly, the various elements, features and steps discussed above, as well as other known equivalents for each such element, feature or step, can be employed in various combinations by one of ordinary skill in this art to perform methods in accordance with the principles described herein. Among the various elements, features, and steps some will be specifically included and others specifically excluded in diverse embodiments. 
     A number of embodiments have been set forth above to illustrate the disclosure. The following claims further set forth what the Applicants regard as their invention.