Patent Publication Number: US-2021177902-A1

Title: Ror-1 specific chimeric antigen receptors and uses thereof

Description:
CROSS-REFERENCE 
     This application is a continuation of International Application No. PCT/US2019/041213, filed on Jul. 10, 2019, which claims the benefit of U.S. Provisional Application No. 62/696,075, filed on Jul. 10, 2018, each of which is entirely incorporated herein by reference in its entirety. 
    
    
     SEQUENCE LISTING 
     The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jul. 8, 2019, is named 50471_716_301_SL.txt and is 360,082 bytes in size. 
     BACKGROUND OF THE DISCLOSURE 
     Recombinant polypeptides such as chimeric polypeptides have been a valuable for research, diagnostic, manufacturing and therapeutic applications. Modified effector cells expressing antigen binding polypeptides such as CARs are useful in the treatment of diseases and disorders such as infectious disease, autoimmune disorders and cancers. 
     INCORPORATION BY REFERENCE 
     All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. 
     SUMMARY OF THE DISCLOSURE 
     Disclosed herein, in certain embodiments, are isolated nucleic acids, vectors, immune effector cells, methods and systems comprising chimeric antigen receptors (CAR). 
     Provided herein is an isolated nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and (e) a CD3 zeta signaling domain. 
     In some embodiments, the CAR comprises at least one of: (a) a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with at least one of amino acid sequences as shown in SEQ ID NOs: 3-14; or (b) a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with at least one of amino acid sequences as shown in SEQ ID NOs: 75-82. In some cases, the ROR-1 antigen binding domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99% or 100% identify with at least one of amino acid sequences as shown in SEQ ID NOs: 15-74. In other cases, the ROR-1 antigen binding domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99% or 100% identify with at least one of amino acid sequences as shown in SEQ ID NOs: 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, and 73. In some examples, the ROR-1 antigen binding domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99% or 100% identify with at least one of amino acid sequences as shown in SEQ ID NOs: 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, and 74. In some embodiments, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 83. In other embodiments, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 84. In some cases, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 85. In some examples, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 86. In other embodiments, the transmembrane domain is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of the amino acid sequences as shown in SEQ ID NOs: 87-88. 
     In some cases, the costimulatory signaling domain comprises 4-1BB. In other embodiments, the costimulatory signaling domain of 4-1BB comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 89. In other cases, the costimulatory signaling domain comprises CD28. In some examples, the costimulatory signaling domain of CD28 comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 90. In some embodiments, the CD3 zeta signaling domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 93. In other embodiments, the isolated nuclei acid further comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NOs: 94-108. 
     In some examples, the isolated nucleic acid further comprises a cell tag. In some embodiments, the cell tag is a truncated epidermal growth factor receptor. In some cases, the truncated epidermal growth factor receptor is HER1t and comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 109. In other embodiments, the truncated epidermal growth factor receptor is HER1t-1 and comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 110. In some embodiments, the cell tag comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 111. In other cases, the cell tag comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 112. In some examples, the isolated nucleic acid further comprises an additional polynucleotide encoding gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. 
     Provided herein is a vector comprising a backbone and a nucleic acid sequence encoding: (1) a cell tag; (2) a cytokine; and (3) a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and (e) a CD3 zeta signaling domain. 
     In some embodiments, the vector is a lentivirus vector, a retroviral vector, or a non-viral vector. In some cases, the cell tag is a truncated epidermal growth factor receptor. In some embodiments, the truncated epidermal growth factor receptor is a HER1t, HER1t-1 or a functional variant thereof. In some examples, the truncated epidermal growth factor receptor comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 109 or SEQ ID NO: 110. In other examples, the cell tag comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 111. In some examples, the cell tag comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 112. 
     In some cases, the cytokine is IL-15. In some embodiments, the IL-15 is a membrane bound IL-15. In some embodiments, the membrane bound IL-15 comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 113. In other cases, the vector further comprises a nucleotide sequence encoding a self-cleaving Thosea asigna virus (T2A) peptide. In some embodiments, the backbone is Sleeping Beauty transposon DNA plasmid. In some examples, the vector further comprises a promoter. In some embodiments, the promoter is hEF1a1. In other embodiments, the CAR comprises at least one of: (a) a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with at least one of amino acid sequences as shown in SEQ ID NOs: 3-14; or (b) a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with at least one of amino acid sequences as shown in SEQ ID NOs: 75-82. 
     In some embodiments, ROR-1 antigen binding domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99% or 100% identify with at least one of amino acid sequences as shown in SEQ ID NOs: 15-74. In some examples, the ROR-1 antigen binding domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99% or 100% identify with at least one of amino acid sequences as shown in SEQ ID NOs: 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, and 73. In other examples, the ROR-1 antigen binding domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99% or 100% identify with at least one of amino acid sequences as shown in SEQ ID NOs: 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, and 74. In some cases, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 83. In other cases, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 84. 
     In some cases, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 8. In other cases, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 86. In some embodiments, the transmembrane domain is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of the amino acid sequences as shown in SEQ ID NOs: 87-88. 
     In some examples, the costimulatory signaling domain comprises 4-1BB. In some embodiments, the costimulatory signaling domain of 4-1BB comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 89. In other embodiments, the CD3 zeta signaling domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 93. In some cases, the vector further comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NOs: 94-108. 
     In some cases, the vector comprises a plasmid. In some embodiments, each vector comprises an expression plasmid. In some embodiments, the non-viral vector is a Sleeping Beauty transposon. In some examples, the vector further comprises an additional vector comprising a polynucleotide encoding gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. 
     Provided herein is an immune effector cell comprising the isolated nucleic acid. In some embodiments, an immune effector cell comprises the vector. 
     Further provided herein is an immune effector cell comprising (1) a cell tag; (2) a cytokine; and (3) a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and (e) a CD3 zeta signaling domain. 
     In some embodiments, the cytokine is IL-15. In some embodiments, the IL-15 is a membrane bound IL-15. In some cases, the membrane bound IL-15 comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 113. In other cases, the cell tag is a truncated epidermal growth factor receptor. In some embodiments, the truncated epidermal growth factor receptor is a HER1t, HER1t-1 or a functional variant thereof. In some cases, the truncated epidermal growth factor receptor comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 109 or SEQ ID NO: 110. In some examples, the cell tag comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 111. In other embodiments, the cell tag comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 112. 
     In some embodiments, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 83. In other embodiments, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 84. In some cases, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 85. In other cases, the spacer is a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 86. 
     In some examples, the cell is a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), or a regulatory T cell. In other examples, the CAR comprises at least one of a polypeptide having amino acid sequences as shown in SEQ ID NOs: 3-14 or 75-82. In some cases, the CAR comprises at least one of a polypeptide having amino acid sequences as shown in SEQ ID NOs: 15-74. In other cases, the immune effector cell further comprises gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. 
     Provided herein is a method for stimulating a T cell-mediated immune response to a target cell population or tissue in a human subject in need thereof, comprising administering to the human subject an effective amount of a cell genetically modified to express a CAR, wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; (e) a CD3 zeta signaling domain; and (f) a truncated epidermal growth factor receptor (HER1t). 
     In some embodiments, the human has been diagnosed with at least one of lung cancer, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, adrenal cancer, melanoma, uterine cancer, testicular cancer, or bladder cancer. In some cases, the human has been diagnosed with non-Hodgkin&#39;s lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM), acute myeloid leukemia (AML), or chronic myeloid leukemia (CML). 
     Provided herein is an isolated nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises: (a) a ROR-1 antigen binding domain with at least one of amino acid sequences of as shown in SEQ ID NO: 3-14, 75-82, or 15-74; (b) a spacer with at least one of amino acid sequences of SEQ ID NOs: 83-86; (c) a costimulatory signaling domain comprising CD28 with the amino acid sequence of SEQ ID NO: 90; (d) a HER1 tag which comprises at least one of HER1t with the amino acid sequence of SEQ ID NO: 109 and HER1t-1 with the amino acid sequence of SEQ ID NO: 110; and (e) a CD3 zeta signaling domain with the amino acid sequence of SEQ ID NO: 93. 
     Provided herein is an isolated nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises: (a) a ROR-1 antigen binding domain with at least one of amino acid sequences as shown in SEQ ID NO: 3-14, 85-82, or 15-74; (b) a spacer with at least one of amino acid sequences of SEQ ID NO: 83-86; (c) a costimulatory signaling domain comprising 4-1BB with the amino acid sequence of SEQ ID NO: 89; (d) a HER1 tag which comprises at least one of HER1t with the amino acid sequence of SEQ ID NO: 109 and HER1t-1 with the amino acid sequence of SEQ ID NO: 110; and (e) a CD3 zeta signaling domain with the amino acid sequence of SEQ ID NO: 93. 
     In some examples, a vector comprises any one or more of the isolated polynucleotides. In some embodiments, the vector is a lentivirus vector, a retroviral vector, or a non-viral vector. In some embodiments, the non-viral vector is a Sleeping Beauty transposon. In other examples, the vector is a plurality of vectors. In some embodiments, the vector further comprises an additional vector comprising a polynucleotide encoding gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. 
     Provided herein is a system for expressing a CAR in an immune effector cell, the system comprising one or more vectors encoding an isolated nucleic acid. In some examples, the immune effector cell is a T cell or NK cell. In some embodiments, the system further comprises a nucleic acid encoding at least one additional gene. In some embodiments, the additional gene comprises a cytokine. In some cases, the cytokine comprises at least one of IL-2, IL-15, IL-12, IL-21, and a fusion of IL-15 and IL-15Ra. In other embodiments, the cytokine is in secreted form. In some embodiments, the cytokine is in membrane bound form. In some embodiments, the system comprises at least one vector. In other cases, the at least one vector is a lentivirus vector, a retroviral vector, or a non-viral vector. In some embodiments, the non-viral vector is a Sleeping Beauty transposon. In some embodiments, the system further comprises a Sleeping Beauty transposase. In some examples, the Sleeping Beauty transposase is SB11, SB100X or SB110. In other examples, the system further comprises an additional vector comprising a polynucleotide encoding gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. In some embodiments, the immune effector cell is a mammalian cell. 
     Provided herein is a system for expressing a CAR in an immune effector cell, the system comprising ( 1 ) a first vector comprising a backbone and a nucleic acid sequence encoding: (a) a cell tag; (b) a cytokine; and (c) a chimeric antigen receptor (CAR), wherein the CAR comprises (i) a ROR-1 antigen binding domain; (ii) a spacer; (iii) a transmembrane domain; (iv) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and (v) a CD3 zeta signaling domain; and (2) a second vector comprising a polynucleotide encoding gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. 
     Provided herein is a method of expressing a CAR in an immune effector cell comprising contacting the immune effector cell with a system. 
     Provided herein is a method of stimulating the proliferation and/or survival of engineered T-cells comprising: (a) obtaining a sample of cells from a subject, the sample comprising T-cells or T-cell progenitors; (b) transfecting the cells with one or more vectors encoding an isolated nucleic acid as provided in any one of claims  1 - 22  and  79 - 80  and a vector encoding a transposase, to provide a population of engineered ROR-1 CAR-expressing T-cells; and (c) optionally culturing the population of ROR-1 CAR T-cells ex vivo for 2 days or less. 
     In some embodiments, the vector further encodes a cytokine and a cell tag. In some cases, the cytokine is a fusion protein comprising IL-15 and IL-15Ra. In other embodiments, the method further comprises an additional vector comprising a polynucleotide encoding gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. 
     In some examples, the DNA binding domain comprises at least one of GAL4 (GAL4 DBD), a LexA DBD, a transcription factor DBD, a steroid/thyroid hormone nuclear receptor superfamily member DBD, a bacterial LacZ DBD, and a yeast DBD. In other embodiments, the DNA binding domain comprises an amino acid sequence as shown in SEQ ID NO: 134. In some embodiments, the transactivation domain comprises at least one of a VP16 transactivation domain and a B42 acidic activator transactivation domain. In other cases, the transactivation domain comprises an amino acid sequence as shown in SEQ ID NO: 131. In some embodiments, at least one of the first nuclear receptor ligand binding domain and the second nuclear receptor ligand binding domain comprises at least one of an ecdysone receptor (EcR), a ubiquitous receptor, an orphan receptor 1, a NER-1, a steroid hormone nuclear receptor 1, a retinoid X receptor interacting protein-15, a liver X receptor (3, a steroid hormone receptor like protein, a liver X receptor, a liver X receptor α, a farnesoid X receptor, a receptor interacting protein 14, and a famesol receptor. 
     In some cases, at least one of the first nuclear receptor ligand binding domain and the second nuclear receptor ligand binding domain comprise any one of amino acid sequences as shown in SEQ ID NOs: 135-136. In some examples, the first gene switch polypeptide comprises a GAL4 DBD fused to an EcR nuclear receptor ligand binding domain, and the second gene switch polypeptide comprises a VP16 transactivation domain fused to a retinoid receptor X (RXR) nuclear receptor ligand binding domain. In some embodiments, the Gal4 DBD fused to the EcR nuclear receptor ligand binding domain comprise an amino acid sequence as shown in any one of SEQ ID NOs: 137-138, and the VP16 transactivation domain fused to the retinoid receptor X (RXR) nuclear receptor ligand binding domain comprises an amino acid sequence as shown in SEQ ID NO: 133. 
     In some embodiments, the linker is a cleavable linker, a ribosome skipping linker sequence or an IRES linker. In some examples, the linker is an IRES linker and said IRES linker has a sequence as shown in any one of SEQ ID NOs: 146-147. In other embodiments, the linker is a cleavable linker or a ribosome skipping linker sequence. In other cases, the cleavable linker or the ribosome skipping linker sequence comprises one or more of a 2A linker, p2A linker, T2A linker, F2A linker, E2A linker, GSG-2A linker, GSG linker (SEQ ID NO: 129), SGSG linker (SEQ ID NO: 130), furinlink linker variants and derivatives thereof. In some embodiments, the cleavable linker or the ribosome skipping linker sequence has a sequence as shown in any one of SEQ ID NOs: 116-126. In some embodiments, at least one of the one or more vectors and the additional vector is a lentivirus vector, a retroviral vector, or a non-viral vector. In some cases, the non-viral vector is a Sleeping Beauty transposon. In some embodiments, the method further comprises a Sleeping Beauty transposase. In some embodiments, the Sleeping Beauty transposase is SB11, SB100X or SB110. 
     Provided herein is a method of culturing engineered T-cells comprising: (a) obtaining a sample of cells from a subject, the sample comprising T-cells or T-cell progenitors; (b) transfecting the cells with one or more vectors encoding an isolated nucleic acid as provided in any one of claims  1 - 22  and  79 - 80  and a vector encoding a transposase, to provide a population of engineered ROR1 CAR-expressing T-cells; and (c) culturing the population of engineered ROR1 CAR-expressing T-cells ex vivo in a medium that selectively enhances proliferation of the engineered ROR1 CAR-expressing T-cells, wherein the engineered ROR1 CAR-expressing T-cells are cultured for no more than 21 days. 
     In some examples, the engineered ROR1 CAR-expressing T-cells are cultured for no more than 14 days. In some cases, the one or more vectors further encodes a cytokine and a cell tag. In some embodiments, the method further comprises an additional vector comprising a polynucleotide encoding gene switch polypeptides for ligand-inducible control of heterologous gene expression, wherein the gene switch polypeptides comprise: (a) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. In other embodiments, the DNA binding domain comprises at least one of GAL4 (GAL4 DBD), a LexA DBD, a transcription factor DBD, a steroid/thyroid hormone nuclear receptor superfamily member DBD, a bacterial LacZ DBD, and a yeast DBD. In some embodiments, the DNA binding domain comprises an amino acid sequence as shown in SEQ ID NO: 134. 
     In other embodiments, the transactivation domain comprises at least one of a VP16 transactivation domain and a B42 acidic activator transactivation domain. In some embodiments, the transactivation domain comprises an amino acid sequence as shown in SEQ ID NO: 131. In some cases, at least one of the first nuclear receptor ligand binding domain and the second nuclear receptor ligand binding domain comprises at least one of an ecdysone receptor (EcR), a ubiquitous receptor, an orphan receptor 1, a NER-1, a steroid hormone nuclear receptor 1, a retinoid X receptor interacting protein-15, a liver X receptor β, a steroid hormone receptor like protein, a liver X receptor, a liver X receptor α, a farnesoid X receptor, a receptor interacting protein 14, and a famesol receptor. In other cases, at least one of the first nuclear receptor ligand binding domain and the second nuclear receptor ligand binding domain comprise any one of amino acid sequences as shown in SEQ ID NOs: 135-136. In some embodiments, the first gene switch polypeptide comprises a GAL4 DBD fused to an EcR nuclear receptor ligand binding domain, and the second gene switch polypeptide comprises a VP16 transactivation domain fused to a retinoid receptor X (RXR) nuclear receptor ligand binding domain. In some examples, the Gal4 DBD fused to the EcR nuclear receptor ligand binding domain comprise an amino acid sequence as shown in any one of SEQ ID NOs: 137-138, and the VP16 transactivation domain fused to the retinoid receptor X (RXR) nuclear receptor ligand binding domain comprises an amino acid sequence as shown in SEQ ID NO: 133. 
     In some cases, the linker is a cleavable linker, a ribosome skipping linker sequence or an IRES linker. In other embodiments, the linker is an IRES linker and said IRES linker has a sequence as shown in any one of SEQ ID NOs: 146-147. In some embodiments, the linker is a cleavable linker or a ribosome skipping linker sequence. In some examples, the cleavable linker or the ribosome skipping linker sequence comprises one or more of a 2A linker, p2A linker, T2A linker, F2A linker, E2A linker, GSG-2A linker, GSG linker (SEQ ID NO: 129), SGSG linker (SEQ ID NO: 130), furinlink linker variants and derivatives thereof. In other examples, the cleavable linker or the ribosome skipping linker sequence has a sequence as shown in any one of SEQ ID NOs: 116-126. In some embodiments, at least one of the one or more vectors, the vector, and the additional vector is a lentivirus vector, a retroviral vector, or a non-viral vector. In some embodiments, the non-viral vector is a Sleeping Beauty transposon. In other embodiments, the method further comprises a Sleeping Beauty transposase. In some cases, the Sleeping Beauty transposase is SB11, SB100X or SB110. In some embodiments, culturing the engineered ROR1 CAR-expressing T-cells in (c) comprises culturing the engineered ROR1 CAR-expressing T-cells in the presence of artificial antigen presenting cells (aAPCs) that stimulate expansion of the engineered ROR1 CAR-T expressing T-cells. In other cases, the aAPCs are engineered K562 cells. In some embodiments, the aAPCs comprises (i) a ROR1 antigen expressed on the engineered CAR cells; (ii) CD64; (ii) CD86; (iii) CD 137L; and/or (v) membrane-bound IL-15, expressed on the surface of the aAPCs. 
     Provided herein is a method of treating cancer in a subject in need thereof comprising administering to the subject one or more doses of an effective amount of engineered T-cells, wherein the engineered T-cells comprise ROR-1 CAR and membrane bound IL-15. 
     In some embodiments, a first dose of an effective amount of engineered T-cells is administered intraperitoneally. In other embodiments, a second dose of an effective amount of engineered T-cells is administered intravenously. In some embodiments, the cancer is non-Hodgkin&#39;s lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM), acute myeloid leukemia (AML), or chronic myeloid leukemia (CML). In some cases, the cancer is lung cancer, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, adrenal cancer, melanoma, uterine cancer, testicular cancer, or bladder cancer. In some examples, the ROR-1 CAR is encoded by any one of sequences as shown in SEQ ID NOs: 3-14, 75-82, or 15-74. In some embodiments, the membrane bound IL-15 is encoded by SEQ ID NO: 260. In some embodiments, the effective amount of engineered T-cells is at least 10 2  cells/kg. In other embodiments, the effective amount of engineered T-cells is at least 10 4  cells/kg. In some cases, the effective amount of engineered T-cells is at least 10 5  cells/kg. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       The features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which: 
         FIGS. 1A-1E  depict exemplary gene expression cassettes for ROR1 CARs and cytokines in different configurations. In certain cases, the ROR1 CAR and/or cytokine can be co-expressed with a cell or kill tag for conditional in vivo ablation. Exemplary gene expression cassettes or combinations thereof for constitutive expression of ROR1 CAR and mbIL-15 can include c+e or d+e. 
         FIGS. 2A-2E  depict exemplary gene expression cassettes for ROR1 CARs and cytokines in different configurations with gene switch components. Exemplary gene expression cassettes or combinations thereof for inducible expression can include a+e, b+e, c+e, or d+e. 
         FIG. 3  depicts an exemplary ROR1 CAR design. ROR1 CAR based on the standard CAR design did not show any expression of ROR1 CAR after gene transfer. Various optimization strategies as described in Example 1 were employed to develop a surface expressed, functional ROR1 CAR. 
         FIG. 4  depicts an illustration of ROR1 CARs with spacers of different lengths. 
         FIG. 5  depicts the combination of signal peptides tested in a ROR1 CAR (murine scFv) construct that utilized conventional CD8a stalk and shows expression of ROR1 CAR (murine scFv) with different signal peptides. Expression of transgenes was measured at Day 1 post nucleofection. Cells were gated as live CD3+ cells. Short CD8a (conventional) stalk does not permit surface expression regardless of signal peptide used (human or mouse). 
         FIG. 6  shows expression of ROR1 CAR (murine scFv) with different combinations of signal peptides and different spacer and spacer lengths. ROR1 CARs utilizing three different longer spacer lengths with strong surface expressions were identified. 
         FIG. 7  shows expression of ROR1 CAR (murine scFv) with CD8a 3X stalk with different signal peptides. Expression of murine scFv based ROR1 CAR with 3X CD8a stalk was improved for certain (mIgGVH, β2M and Azurocidin) signal peptides. 
         FIG. 8  shows different ROR 1 CAR (murine scFv) with various combinations of stalk, intracellular domain and orientations of the VH/VL chains evaluated and expression of ROR 1 CAR (murine scFv) with various combinations of stalk, intracellular domain and orientations of the VH/VL chains. As observed, reversing orientation from VL-VH to VH-VL enables surface expression form hGMCSFR and hIGHV3-23 signal peptides. 
         FIG. 9A  and  FIG. 9B  show specificity of ROR1(murine scFv)-CD8-3x stalk.CD28z CAR-T cells in various tumor cell lines as measured in CD107a degranulation assay and IFN-α expression assay. 
         FIG. 10A  shows quantitative analysis of JeKo-1 tumor burden as measured by in vivo bioluminescence (IVIS) imaging at day 7 post CAR-T treatment. NSG mice (N=5-7 mice per group) were administered with JeKo tumor cell line via i.p. injection on Day 0. Tumor bearing mice were treated with different hROR1 CAR-T cells treatment via single i.p. injection seven days after tumor cell administration and tumor burden was quantified via IVIS through the course of treatment. Data shown are mean±SEM. 
         FIG. 10B  shows tumor burden pre-treatment. 
         FIG. 11  shows quantitative analysis of JeKo-1 tumor burden as measured by in vivo bioluminescence (IVIS) imaging (as described above) at day 36. 
         FIG. 12  shows quantification of human CD3+ T cells in peripheral blood of tumor bearing NSG mice treated with various hROR1 CAR-T cells. The CD3+ T cell expansion in blood was measured at days 15, 22, 29, 36, 43 and 50. 
         FIG. 13A  and  FIG. 13B  demonstrates that ROR1+ tumor cell lines were equally killed by hROR1 CAR T cells co-expressing constitutive or RTS-mbIL-15 in vitro. 
         FIG. 14  demonstrates that administration of hROR1 CAR RTS-mbIL-15-T cells+veledimex promotes anti-tumor effect in a JeKo-1 xenograft mouse model in a dose-dependent manner. 
     
    
    
     DETAILED DESCRIPTION OF THE DISCLOSURE 
     The following description and examples illustrate embodiments of the invention in detail. It is to be understood that this invention is not limited to the particular embodiments described herein and as such can vary. Those of skill in the art will recognize that there are numerous variations and modifications of this invention, which are encompassed within its scope. 
     All terms are intended to be understood as they would be understood by a person skilled in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure pertains. 
     The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. 
     Although various features of the invention can be described in the context of a single embodiment, the features can also be provided separately or in any suitable combination. Conversely, although the invention can be described herein in the context of separate embodiments for clarity, the invention can also be implemented in a single embodiment. 
     The following definitions supplement those in the art and are directed to the current application and are not to be imputed to any related or unrelated case, e.g., to any commonly owned patent or application. Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the present disclosure, the preferred materials and methods are described herein. Accordingly, the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. 
     In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting. 
     Reference in the specification to “some embodiments,” “an embodiment,” “one embodiment” or “other embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least some embodiments, but not necessarily all embodiments, of the inventions. 
     As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the invention, and vice versa. Furthermore, compositions of the invention can be used to achieve methods of the invention. 
     The term “about” in relation to a reference numerical value and its grammatical equivalents as used herein can include the numerical value itself and a range of values plus or minus 10% from that numerical value. For example, the amount “about 10” includes 10 and any amounts from 9 to 11. For example, the term “about” in relation to a reference numerical value can also include a range of values plus or minus 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% from that value. 
     By “isolated” is meant the removal of a nucleic acid from its natural environment. By “purified” is meant that a given nucleic acid, whether one that has been removed from nature (including genomic DNA and mRNA) or synthesized (including cDNA) and/or amplified under laboratory conditions, has been increased in purity, wherein “purity” is a relative term, not “absolute purity.” It is to be understood, however, that nucleic acids and proteins can be formulated with diluents or adjuvants and still for practical purposes be isolated. For example, nucleic acids typically are mixed with an acceptable carrier or diluent when used for introduction into cells. 
     “Polynucleotide” or “oligonucleotide” as used herein refers to a polymeric form of nucleotides of any length, either ribonucleotides or deoxyribonucleotides. This term refers only to the primary structure of the molecule. Thus, this term includes double and single stranded DNA, triplex DNA, as well as double and single stranded RNA. It also includes modified, for example, by methylation and/or by capping, and unmodified forms of the polynucleotide. The term is also meant to include molecules that include non-naturally occurring or synthetic nucleotides as well as nucleotide analogs. 
     “Polypeptide” is used interchangeably with the terms “polypeptides” and “protein(s),” and refers to a polymer of amino acid residues. A “mature protein” is a protein which is full-length and which, optionally, includes glycosylation or other modifications typical for the protein in a given cellular environment. 
     Nucleic acids and/or nucleic acid sequences are “homologous” when they are derived, naturally or artificially, from a common ancestral nucleic acid or nucleic acid sequence. Proteins and/or protein sequences are homologous when their encoding DNAs are derived, naturally or artificially, from a common ancestral nucleic acid or nucleic acid sequence. The homologous molecules can be termed homologs. For example, any naturally occurring proteins, as described herein, can be modified by any available mutagenesis method. When expressed, this mutagenized nucleic acid encodes a polypeptide that is homologous to the protein encoded by the original nucleic acid. Homology is generally inferred from sequence identity between two or more nucleic acids or proteins (or sequences thereof). The precise percentage of identity between sequences that is useful in establishing homology varies with the nucleic acid and protein at issue, but as little as 25% sequence identity is routinely used to establish homology. Higher levels of sequence identity, e.g., 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 99% or more can also be used to establish homology. 
     The terms “identical” or “sequence identity” in the context of two nucleic acid sequences or amino acid sequences of polypeptides refers to the residues in the two sequences which are the same when aligned for maximum correspondence over a specified comparison window. In one class of embodiments, the polypeptides herein are at least 80%, 85%, 90%, 98% 99% or 100% identical to a reference polypeptide, or a fragment thereof, e.g., as measured by BLASTP (or CLUSTAL, or any other available alignment software) using default parameters. Similarly, nucleic acids can also be described with reference to a starting nucleic acid, e.g., they can be 50%, 60%, 70%, 75%, 80%, 85%, 90%, 98%, 99% or 100% identical to a reference nucleic acid or a fragment thereof, e.g., as measured by BLASTN (or CLUSTAL, or any other available alignment software) using default parameters. When one molecule is the to have certain percentage of sequence identity with a larger molecule, it means that when the two molecules are optimally aligned, the percentage of residues in the smaller molecule finds a match residue in the larger molecule in accordance with the order by which the two molecules are optimally aligned. 
     “Transposon” or “transposable element” (TE) is a vector DNA sequence that can change its position within the genome, sometimes creating or reversing mutations and altering the cell&#39;s genome size. Transposition often results in duplication of the TE. Class I TEs are copied in two stages: first, they are transcribed from DNA to RNA, and the RNA produced is then reverse transcribed to DNA. This copied DNA is then inserted at a new position into the genome. The reverse transcription step is catalyzed by a reverse transcriptase, which can be encoded by the TE itself. The characteristics of retrotransposons are similar to retroviruses, such as HIV. The cut-and-paste transposition mechanism of class II TEs does not involve an RNA intermediate. The transpositions are catalyzed by several transposase enzymes. Some transposases non-specifically bind to any target site in DNA, whereas others bind to specific DNA sequence targets. The transposase makes a staggered cut at the target site resulting in single-strand 5′ or 3′ DNA overhangs (sticky ends). This step cuts out the DNA transposon, which is then ligated into a new target site; this process involves activity of a DNA polymerase that fills in gaps and of a DNA ligase that closes the sugar-phosphate backbone. This results in duplication of the target site. The insertion sites of DNA transposons can be identified by short direct repeats which can be created by the staggered cut in the target DNA and filling in by DNA polymerase, followed by a series of inverted repeats important for the TE excision by transposase. Cut-and-paste TEs can be duplicated if their transposition takes place during S phase of the cell cycle when a donor site has already been replicated, but a target site has not yet been replicated. Transposition can be classified as either “autonomous” or “non-autonomous” in both Class I and Class II TEs. Autonomous TEs can move by themselves while non-autonomous TEs require the presence of another TE to move. This is often because non-autonomous TEs lack transposase (for class II) or reverse transcriptase (for class I). 
     “Transposase” refers an enzyme that binds to the end of a transposon and catalyzes the movement of the transposon to another part of the genome by a cut and paste mechanism or a replicative transposition mechanism. In some embodiments, the transposase&#39;s catalytic activity can be utilized to move gene(s) from a vector to the genome. 
     The nucleic acid sequences and vectors disclosed or contemplated herein can be introduced into a cell by “transfection,” “transformation,” “nucleofection” or “transduction.” “Transfection,” “transformation,” or “transduction,” as used herein, refer to the introduction of one or more exogenous polynucleotides into a host cell by using physical or chemical methods. Many transfection techniques are known in the art and include, for example, calcium phosphate DNA co-precipitation (see, e.g., Murray E. J. (ed.), Methods in Molecular Biology, Vol. 7, Gene Transfer and Expression Protocols, Humana Press (1991)); DEAE-dextran; electroporation; cationic liposome-mediated transfection; tungsten particle-facilitated microparticle bombardment (Johnston, Nature, 346: 776-777 (1990)); and strontium phosphate DNA co-precipitation (Brash et al., Mol. Cell Biol., 7: 2031-2034 (1987)); and nucleofection (Trompeter et al., J. Immunol. Methods 274:245-256 (2003). Phage or viral vectors can be introduced into host cells, after growth of infectious particles in suitable packaging cells, many of which are commercially available. 
     “Promoter” refers to a region of a polynucleotide that initiates transcription of a coding sequence. Promoters are located near the transcription start sites of genes, on the same strand and upstream on the DNA (towards the 5′ region of the sense strand). Some promoters are constitutive as they are active in all circumstances in the cell, while others are regulated becoming active in response to specific stimuli, e.g., an inducible promoter. 
     The term “promoter activity” refers to the extent of expression of nucleotide sequence that is operably linked to the promoter whose activity is being measured. Promoter activity can be measured directly by determining the amount of RNA transcript produced, for example by Northern blot analysis or indirectly by determining the amount of product coded for by the linked nucleic acid sequence, such as a reporter nucleic acid sequence linked to the promoter. 
     “Inducible promoter” as used herein refers to a promoter which is induced into activity by the presence or absence of transcriptional regulators, e.g., biotic or abiotic factors. Inducible promoters are useful because the expression of genes operably linked to them can be turned on or off at certain stages of development of an organism or in a particular tissue. Examples of inducible promoters are alcohol-regulated promoters, tetracycline-regulated promoters, steroid-regulated promoters, metal-regulated promoters, pathogenesis-regulated promoters, temperature-regulated promoters and light-regulated promoters. In one embodiment, the inducible promoter is part of a genetic switch. 
     The term “enhancer,” as used herein, refers to a DNA sequence that increases transcription of, for example, a nucleic acid sequence to which it is operably linked. Enhancers can be located many kilobases away from the coding region of the nucleic acid sequence and can mediate the binding of regulatory factors, patterns of DNA methylation, or changes in DNA structure. A large number of enhancers from a variety of different sources are well known in the art and are available as or within cloned polynucleotides (from, e.g., depositories such as the ATCC as well as other commercial or individual sources). A number of polynucleotides comprising promoters (such as the commonly-used CMV promoter) also comprise enhancer sequences. Enhancers can be located upstream, within, or downstream of coding sequences. The term “Ig enhancers” refers to enhancer elements derived from enhancer regions mapped within the immunoglobulin (Ig) locus (such enhancers include for example, the heavy chain (mu) 5′ enhancers, light chain (kappa) 5′ enhancers, kappa and mu intronic enhancers, and 3′ enhancers (see generally Paul W. E. (ed), Fundamental Immunology, 3rd Edition, Raven Press, New York (1993), pages 353-363; and U.S. Pat. No. 5,885,827). 
     “Coding sequence” as used herein refers to a segment of a polynucleotide that codes for a polypeptide. The region or sequence is bounded nearer the 5′ end by a start codon and nearer the 3′ end with a stop codon. Coding sequences can also be referred to as open reading frames. 
     “Operably linked” as used herein refers to refers to the physical and/or functional linkage of a DNA segment to another DNA segment in such a way as to allow the segments to function in their intended manners. A DNA sequence encoding a gene product is operably linked to a regulatory sequence when it is linked to the regulatory sequence, such as, for example, promoters, enhancers and/or silencers, in a manner which allows modulation of transcription of the DNA sequence, directly or indirectly. For example, a DNA sequence is operably linked to a promoter when it is ligated to the promoter downstream with respect to the transcription initiation site of the promoter, in the correct reading frame with respect to the transcription initiation site and allows transcription elongation to proceed through the DNA sequence. An enhancer or silencer is operably linked to a DNA sequence coding for a gene product when it is ligated to the DNA sequence in such a manner as to increase or decrease, respectively, the transcription of the DNA sequence. Enhancers and silencers can be located upstream, downstream or embedded within the coding regions of the DNA sequence. A DNA for a signal sequence is operably linked to DNA coding for a polypeptide if the signal sequence is expressed as a preprotein that participates in the secretion of the polypeptide. Linkage of DNA sequences to regulatory sequences is typically accomplished by ligation at suitable restriction sites or via adapters or linkers inserted in the sequence using restriction endonucleases known to one of skill in the art. 
     The term “transcriptional regulator” refers to a biochemical element that acts to prevent or inhibit the transcription of a promoter-driven DNA sequence under certain environmental conditions (e.g., a repressor or nuclear inhibitory protein), or to permit or stimulate the transcription of the promoter-driven DNA sequence under certain environmental conditions (e.g., an inducer or an enhancer). 
     The term “induction” refers to an increase in nucleic acid sequence transcription, promoter activity and/or expression brought about by a transcriptional regulator, relative to some basal level of transcription. 
     A “target” gene or “heterologous” gene, or “gene of interest (GOI)” refers to a gene introduced into the host cell by gene transfer. 
     “Recombinase” as used herein refers to a group of enzymes that can facilitate site-specific recombination between defined sites, where the sites are physically separated on a single DNA molecule or where the sites reside on separate DNA molecules. The DNA sequences of the defined recombination sites are not necessarily identical. Initiation of recombination depends on protein-DNA interaction, within the group there are large number of proteins that catalyze phage integration and excision (e.g., λ integrase, .ϕC31), resolution of circular plasmids (e.g., Tn3, gamma delta, Cre, Flp), DNA inversion for expression of alternate genes (e.g., Hin, Gin, Pin), assembly of genes during development (e.g.,  Anabaena  nitrogen fixation genes), and transposition (e.g., IS607 transposon). Most site-specific recombinases fall into one of the two families, based on evolutionary and mechanistic relatedness. These are λ integrase family or tyrosine recombinases (e.g., Cre, Flp, Xer D) and resolvase/integrase family or serine recombinase family (e.g., ϕC31, TP901-1, Tn3, gamma delta). 
     “Recombination attachment sites” are specific polynucleotide sequences that are recognized by the recombinase enzymes described herein. Typically, two different sites are involved (termed “complementary sites”), one present in the target nucleic acid (e.g., a chromosome or episome of a eukaryote or prokaryote) and another on the nucleic acid that is to be integrated at the target recombination site. The terms “attB” and “attP,” which refer to attachment (or recombination) sites originally from a bacterial target and a phage donor, respectively, are used herein although recombination sites for particular enzymes can have different names. The recombination sites typically include left and right arms separated by a core or spacer region. Thus, an attB recombination site consists of BOB′, where B and B′ are the left and right arms, respectively, and O is the core region. Similarly, attP is POP′, where P and P′ are the arms and O is again the core region. Upon recombination between the attB and attP sites, and concomitant integration of a nucleic acid at the target, the recombination sites that flank the integrated DNA are referred to as “attL” and “attR.” The attL and attR sites, using the terminology above, thus consist of BOP′ and POB′, respectively. In some representations herein, the “O” is omitted and attB and attP, for example, are designated as BB′ and PP′, respectively. 
     An “expression vector” or “vector” is any genetic element, e.g., a plasmid, chromosome, virus, transposon, behaving either as an autonomous unit of polynucleotide replication within a cell. (i.e. capable of replication under its own control) or being rendered capable of replication by insertion into a host cell chromosome, having attached to it another polynucleotide segment, so as to bring about the replication and/or expression of the attached segment. Suitable vectors include, but are not limited to, plasmids, transposons, bacteriophages and cosmids. Vectors can contain polynucleotide sequences which are necessary to effect ligation or insertion of the vector into a desired host cell and to effect the expression of the attached segment. Such sequences differ depending on the host organism; they include promoter sequences to effect transcription, enhancer sequences to increase transcription, ribosomal binding site sequences and transcription and translation termination sequences. Alternatively, expression vectors can be capable of directly expressing nucleic acid sequence products encoded therein without ligation or integration of the vector into host cell DNA sequences. 
     Vector also can comprise a “selectable marker gene.” The term “selectable marker gene,” as used herein, refers to a nucleic acid sequence that allows cells expressing the nucleic acid sequence to be specifically selected for or against, in the presence of a corresponding selective agent. Suitable selectable marker genes are known in the art and described in, e.g., International Patent Application Publications WO 1992/08796 and WO 1994/28143; Wigler et al., Proc. Natl. Acad. Sci. USA, 77: 3567 (1980); O&#39;Hare et al., Proc. Natl. Acad. Sci. USA, 78: 1527 (1981); Mulligan &amp; Berg, Proc. Natl. Acad. Sci. USA, 78: 2072 (1981); Colberre-Garapin et al., J. Mol. Biol., 150:1 (1981); Santerre et al., Gene, 30: 147 (1984); Kent et al., Science, 237: 901-903 (1987); Wigler et al., Cell, 11: 223 (1977); Szybalska &amp; Szybalski, Proc. Natl. Acad. Sci. USA, 48: 2026 (1962); Lowy et al., Cell, 22: 817 (1980); and U.S. Pat. Nos. 5,122,464 and 5,770,359. 
     In some embodiments, the vector is an “episomal expression vector” or “episome,” which is able to replicate in a host cell, and persists as an extrachromosomal segment of DNA within the host cell in the presence of appropriate selective pressure (see, e.g., Conese et al., Gene Therapy, 11:1735-1742 (2004)). Representative commercially available episomal expression vectors include, but are not limited to, episomal plasmids that utilize Epstein Barr Nuclear Antigen 1 (EBNA1) and the Epstein Barr Virus (EBV) origin of replication (oriP). The vectors pREP4, pCEP4, pREP7, and pcDNA3.1 from Invitrogen (Carlsbad, Calif.) and pBK-CMV from Stratagene (La Jolla, Calif.) represent non-limiting examples of an episomal vector that uses T-antigen and the SV40 origin of replication in lieu of EBNA1 and oriP. 
     “Cancer cell” refers to a cell undergoing early, intermediate or advanced stages of multi-step neoplastic progression as previously described (Pitot et al., Fundamentals of Oncology, 15-28 (1978)). This includes cells in early, intermediate and advanced stages of neoplastic progression including “pre-neoplastic” cells (i.e., “hyperplastic” cells and dysplastic cells), and neoplastic cells in advanced stages of neoplastic progression of a dysplastic cell. 
     “Metastatic” cancer cell refers to a cancer cell that is translocated from a primary cancer site (i.e., a location where the cancer cell initially formed from a normal, hyperplastic or dysplastic cell) to a site other than the primary site, where the translocated cancer cell lodges and proliferates. 
     “Cancer” refers to a plurality of cancer cells that may or may not be metastatic, such as ovarian cancer, breast cancer, lung cancer, prostate cancer, cervical cancer, pancreatic cancer, colon cancer, stomach cancer, esophagus cancer, mouth cancer, tongue cancer, gum cancer, skin cancer (e.g., melanoma, basal cell carcinoma, Kaposi&#39;s sarcoma, etc.), muscle cancer, heart cancer, liver cancer, bronchial cancer, cartilage cancer, bone cancer, testis cancer, kidney cancer, endometrium cancer, uterus cancer, bladder cancer, bone marrow cancer, lymphoma cancer, spleen cancer, thymus cancer, thyroid cancer, brain cancer, neuron cancer, mesothelioma, gall bladder cancer, ocular cancer (e.g., cancer of the cornea, cancer of uvea, cancer of the choroids, cancer of the macula, vitreous humor cancer, etc.), joint cancer (such as synovium cancer), glioblastoma, lymphoma, leukemia, non-Hodgkin&#39;s lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM), acute myeloid leukemia (AML), or chronic myeloid leukemia (CML). 
     ROR-1 
     ROR1 is a transmembrane protein within the receptor tyrosine kinase (RTK) family. The ROR1 gene encodes two well-defined isoforms: a short 393 amino acid (aa) intracellular protein (isoform 2) and a long 937 aa type-1 transmembrane protein (isoform 1). The long cell surface isoform is expressed on primary human B-chronic lymphocytic leukemia (B-CLL) and mantle cell lymphomas, a subset of B-acute lymphocytic leukemia, and many tumors, including those associated with a metastatic phenotype. 
     ROR1 is principally expressed during embryonic development but its expression attenuates during fetal development. However, ROR1 is aberrantly expressed by some B-cell malignancies such as but not limited to, lymphomas, CLL, and B-ALL, and by many solid tumor malignancies, such as but not limited to, adrenal, bladder, breast, colon, lung, pancreas, prostate, ovary, skin, testes, uterus, and neuroblastoma. 
     Chimeric Antigen Receptors 
     In embodiments described herein, a CAR can comprise an extracellular antibody-derived single-chain variable domain (scFv) for target recognition, wherein the scFv can be connected by a flexible linker to a transmembrane domain and/or an intracellular signaling domain(s) that includes, for instance, CD3 for T-cell activation. Normally when T cells are activated in vivo they receive a primary antigen induced TCR signal with secondary costimulatory signaling from CD28 that induces the production of cytokines (i.e., IL-2 and IL-21), which then feed back into the signaling loop in an autocrine/paracrine fashion. As such, CARs can include a signaling domain, for instance, a CD28 cytoplasmic signaling domain or other costimulatory molecule signaling domains such as 4-1BB signaling domain. Chimeric CD28 co-stimulation improves T-cell persistence by up-regulation of anti-apoptotic molecules and production of IL-2, as well as expanding T cells derived from peripheral blood mononuclear cells (PBMC). 
     In one embodiment, CARs are fusions of single-chain variable fragments (scFv) derived from monoclonal antibodies specific for various epitopes of ROR-1 for example, fused to transmembrane domain and CD3-zeta endodomain. Such molecules result in the transmission of a zeta signal in response to recognition by the scFv of its target. 
     In an embodiment, a CAR can have an ectodomain (extracellular), a transmembrane domain and an endodomain (intracellular). In one embodiment of the CAR ectodomain, a signal peptide directs the nascent protein into the endoplasmic reticulum. This is if the receptor is to be glycosylated and anchored in the cell membrane for example. Any eukaryotic signal peptide sequence is envisaged to be functional. Generally, the signal peptide natively attached to the amino-terminal most component is used (e.g., in a scFv with orientation light chain-linker-heavy chain, the native signal of the light-chain is used). In embodiments, the signal peptide is GM-CSFRa (SEQ ID NO: 94) or IgK (SEQ ID NO: 95). Other signal peptides that can be used include signal peptides from CD8alpha (SEQ ID NO: 97) and CD28. In one embodiment, the signal peptide is Mouse Ig VH region 3 (SEQ ID NO: 101), Azurocidin (SEQ ID NO: 103), IGHV3-23 (SEQ ID NO: 106), IGKV1-D33 (HuL1) (SEQ ID NO: 107) or IGKV1-D33 (L14F) (HuH7) (SEQ ID NO: 108). 
     The antigen recognition domain can be a scFv. There can, however, be alternatives. An antigen recognition domain from native T-cell receptor (TCR) alpha and beta single chains are envisaged, as they have simple ectodomains (e.g. CD4 ectodomain) and as well as other recognition components such as a linked e.g., cytokine (which leads to recognition of cells bearing the cytokine receptor). Almost anything that binds a given target, such as e.g., viral associated antigen, with high affinity can be used as an antigen recognition region. 
     In general, CARs exist in a dimerized form and are expressed as a fusion protein that links the extracellular scFv (VH linked to VL) region, a spacer, a transmembrane domain, and intracellular signaling motifs. The endodomain of the first generation CAR induces T cell activation solely through CD3-ζ signaling. The second generation CAR provides activation signaling through CD3-ζ and CD28, or other endodomains such as 4-1BB or OX40. The 3rd generation CAR activates T cells via a CD3-ζ-containing combination of three signaling motifs such as CD28, 4-1BB, or OX40. 
     In embodiments, the present invention provides chimeric antigen receptor (CAR) comprising an extracellular domain, a transmembrane domain and an intracellular signaling domain. In embodiments, the extracellular domain comprises a target-specific binding element otherwise referred to as an antigen binding moiety or scFv and a spacer. In embodiments, the intracellular signaling domain or otherwise the cytoplasmic signaling domain comprises, a costimulatory signaling region and a zeta chain portion. 
     The costimulatory signaling region refers to a portion of the CAR comprising the intracellular signaling domain of a costimulatory molecule. Costimulatory molecules are cell surface molecules other than antigens receptors or their ligands that are required for an efficient response of lymphocytes to antigen. 
     In embodiments, between the extracellular domain and the transmembrane domain of the CAR, there is incorporated a stalk domain or stalk region. As used herein, the term “stalk domain” or “stalk region” generally means any oligonucleotide- or polypeptide that functions to link the transmembrane domain to, either the scFv or, the cytoplasmic domain in the polypeptide chain. A stalk domain can include a flexible hinge such as a Fc hinge and optionally one or two constant domains of Fc. In some instances, the stalk region comprises the hinge region from IgG1. In alternative instances, the stalk region comprises the CH2CH3 region of immunoglobulin and optionally portions of CD3. In some cases, the stalk region comprises a CD8a hinge region (SEQ ID NO: 83), an IgG4-Fc 12 amino acid hinge region (ESKYGPPCPPCP (SEQ ID NO: 285)) or IgG4 hinge regions as described in WO/2016/073755. 
     In other embodiments, between the extracellular domain and the transmembrane domain of the CAR, there is an incorporated spacer. A spacer can comprise a stalk region and a stalk extension region as depicted in  FIGS. 3 and 4 . In some embodiments, the spacer extends the distance between different domains of a chimeric polypeptide resulting in improved expression or functional activity of the polypeptide compared to an otherwise identical polypeptide lacking the spacer. In some instances, a spacer comprises any polypeptide that functions to link the transmembrane region to, either the extracellular region or, the cytoplasmic region in the chimeric polypeptide. In some embodiments, the spacer is flexible enough to allow the antigen or ligand-binding region to align in different orientations to facilitate antigen or ligand receptor recognition. 
     In some embodiments, the stalk region can be from about 20 to about 300 amino acids in length and comprises at least one dimerization site, and a stalk extension region can comprise from about 1 to about 10 times the length of the stalk region as measured by number of amino acids. 
     In some cases, a stalk region can be about 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 or greater amino acids in length. In other cases, the stalk region can be about: 100, 125, 150, 175, 200, 225, 250, 275 or 300 amino acids in length. 
     In one embodiment, a spacer can include a single stalk region. In another embodiment, a spacer can comprise a stalk region (designated as “5”) and stalk extension region(s), which is herein designated as “S′n.” For example, a spacer can comprise one (1) stalk region and S′n, wherein n can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In further embodiments, the stalk region can be linked to stalk extension region S′n via a linker. In one embodiment, when the CAR is a ROR1 CAR, n is not 0. 
     In some cases, a stalk extension region can comprise from about 1 to about 10 times the length of the stalk region as measured by number of amino acids. For example, a stalk extension region can comprise about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times the length of the stalk region as measured by number of amino acids. In some cases, a stalk extension region can comprise greater than 10 times the length of the stalk region as measured by number of amino acids. In some examples, a stalk extension region can comprise up to 2 times the length of the stalk region as measured by number of amino acids but comprise fewer dimerization sites than the stalk region. 
     A stalk extension region of a subject antigen-binding polypeptide can contain at least one fewer dimerization site as compared to a stalk region. For example, if a stalk region comprises two dimerization sites, a stalk extension region can comprise one or zero dimerization sites. As another example, if a stalk region comprises one dimerization site, a stalk extension region can comprise zero dimerization sites. In some examples, a stalk extension region lacks a dimerization site. In some examples, a stalk extension region can comprise up to 2 times the length of the stalk region as measured by number of amino acids but comprise no dimerization sites. In some examples, a stalk extension region can comprise up to 3 times the length of the stalk region as measured by number of amino acids but comprise no dimerization sites. In some examples, a stalk extension region can comprise up to 4 times the length of the stalk region as measured by number of amino acids but comprise zero dimerization sites. In some cases, one or more dimerization site(s) can be membrane proximal. In other cases, one or more dimerization site(s) can be membrane distal. 
     Each of the stalk extension regions can, in some examples, be from about 20 to about 60 amino acids in length. In other examples, stalk extension regions can be about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, greater amino acids in length, or any integer within or outside of that range. In some cases, each stalk extension region has a sequence which has at least about 60% identity to the stalk region. In some examples, each stalk extension region has a sequence which has at least about 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or greater identity to the stalk region. 
     The transmembrane domain can be derived from either a natural or a synthetic source. Where the source is natural, the domain can be derived from any membrane-bound or transmembrane protein. Suitable transmembrane domains can include the transmembrane region(s) of alpha, beta or zeta chain of the T-cell receptor; or a transmembrane region from CD28, CD3 epsilon, CD3 CD45, CD4, CD5, CD8alpha, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 or CD154. Alternatively the transmembrane domain can be synthetic, and can comprise hydrophobic residues such as leucine and valine. In some embodiments, a triplet of phenylalanine, tryptophan and valine is found at one or both termini of a synthetic transmembrane domain. Optionally, a short oligonucleotide or polypeptide linker, in some embodiments, between 2 and 10 amino acids in length can form the linkage between the transmembrane domain and the cytoplasmic signaling domain of a CAR. In some embodiments, the linker is a glycine-serine linker. In some embodiments, the transmembrane domain comprises a CD8α transmembrane domain or a CD3 transmembrane domain. In some embodiments, the transmembrane domain comprises a CD8a transmembrane domain. In other embodiments, the transmembrane domain comprises a CD3 transmembrane domain. 
     The intracellular domain can comprise one or more costimulatory domains. Exemplary costimulatory domains include, but are not limited to, CD8, CD27, CD28, 4-1BB (CD137), ICOS, DAP10, DAP12, OX40 (CD134), CD3-zeta or fragment or combination thereof. In some instances, a CAR described herein comprises one or more, or two or more of costimulatory domains selected from CD8, CD27, CD28, 4-1BB (CD137), ICOS, DAP10, DAP12, OX40 (CD134) or fragment or combination thereof. In some instances, a CAR described herein comprises one or more, or two or more of costimulatory domains selected from CD27, CD28, 4-1BB (CD137), ICOS, OX40 (CD134) or fragment or combination thereof. In some instances, a CAR described herein comprises one or more, or two or more of costimulatory domains selected from CD8, CD28, 4-1BB (CD137), DAP10, DAP12 or fragment or combination thereof. In some instances, a CAR described herein comprises one or more, or two or more of costimulatory domains selected from CD28, 4-1BB (CD137), or fragment or combination thereof. In some instances, a CAR described herein comprises costimulatory domains CD28 and 4-1BB (CD137) or their respective fragments thereof. In some instances, a CAR described herein comprises costimulatory domains CD28 and OX40 (CD134) or their respective fragments thereof. In some instances, a CAR described herein comprises costimulatory domains CD8 and CD28 or their respective fragments thereof. In some instances, a CAR described herein comprises costimulatory domains CD28 or a fragment thereof. In some instances, a CAR described herein comprises costimulatory domains 4-1BB (CD137) or a fragment thereof. In some instances, a CAR described herein comprises costimulatory domains OX40 (CD134) or a fragment thereof. In some instances, a CAR described herein comprises costimulatory domains CD8 or a fragment thereof. In some instances, a CAR described herein comprises at least one costimulatory domain DAP10 or a fragment thereof. In some instances, a CAR described herein comprises at least one costimulatory domain DAP12 or a fragment thereof. 
     The intracellular signaling domain, also known as cytoplasmic domain, of the CAR of the present disclosure, is responsible for activation of at least one of the normal effector functions of the immune cell in which the CAR has been placed. The term “effector function” refers to a specialized function of a cell. Effector function of a T cell, for example, can be cytolytic activity or helper activity including the secretion of cytokines. Thus, the term “intracellular signaling domain” refers to the portion of a protein which transduces the effector function signal and directs the cell to perform a specialized function. While usually the entire intracellular signaling domain can be employed, in many cases it is not necessary to use the entire chain. To the extent that a truncated portion of the intracellular signaling domain is used, such truncated portion can be used in place of the intact chain as long as it transduces the effector function signal. The term intracellular signaling domain is thus meant to include any truncated portion of the intracellular signaling domain sufficient to transduce the effector function signal. In some embodiments, the intracellular domain further comprises a signaling domain for T-cell activation. In some instances, the signaling domain for T-cell activation comprises a domain derived from TCR zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b or CD66d. In some cases, the signaling domain for T-cell activation comprises a domain derived from CD3. 
     In embodiments, provided herein is an isolated nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a stalk domain; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; (e) a CD3 zeta signaling domain; and optionally (f) a truncated epidermal growth factor receptor (HER1t or HER1t1). 
     Included in the scope of the invention are nucleic acid sequences that encode functional portions of the CAR described herein. 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 a nucleic acid sequence encoding the parent CAR, a nucleic acid sequence encoding a functional portion of the CAR can encode a protein comprising, for example, about 10%, 25%, 30%, 50%, 68%, 80%, 90%, 95%, or more, of the parent CAR. 
     In embodiments, the CAR contains additional amino acids at the amino or carboxy terminus of the portion, or at both termini, which additional amino acids are not found in the amino acid sequence of the parent CAR. Desirably, the additional amino acids do not interfere with the biological function of the functional portion, e.g., recognize target cells, detect cancer, treat or prevent cancer, etc. More desirably, the additional amino acids enhance the biological activity of the CAR, as compared to the biological activity of the parent CAR. 
     The term “functional variant,” as used herein, refers to a polypeptide, or a protein having substantial or significant sequence identity or similarity to the reference polypeptide, and retains the biological activity of the reference polypeptide of which it is a variant. Functional variants encompass, for example, those variants of the CAR described herein (the parent CAR) that retain the ability to recognize target cells to a similar extent, the same extent, or to a higher extent, as the parent CAR. In reference to a nucleic acid sequence encoding the parent CAR, a nucleic acid sequence encoding a functional variant of the CAR can be for example, about 10% identical, about 25% identical, about 30% identical, about 50% identical, about 65% identical, about 80% identical, about 90% identical, about 95% identical, or about 99% identical to the nucleic acid sequence encoding the parent CAR. 
     A CAR described herein include (including functional portions and functional variants thereof) glycosylated, amidated, carboxylated, phosphorylated, esterified, N-acylated, cyclized via, e.g., a disulfide bridge, or converted into an acid addition salt and/or optionally dimerized or polymerized, or conjugated. 
     Antigen Binding Moiety 
     In embodiments, a CAR described herein comprises a target-specific binding element otherwise referred to as an antigen-binding moiety. In embodiments, a CAR described herein engineered to target an antigen of interest by way of engineering a desired antigen-binding moiety that specifically binds to an antigen on a cell. 
     In embodiments, the antigen binding moiety of a CAR described herein is specific to ROR-1 (ROR-1 CAR). The ROR-1-specific CAR, when expressed on the cell surface, redirects the specificity of T cells to human ROR-1. In embodiments, the antigen binding domain comprises a single chain antibody fragment (scFv) comprising a variable domain light chain (VL) and variable domain heavy chain (VH) of a target antigen specific monoclonal anti-ROR-1 antibody joined by a flexible linker, such as a glycine-serine linker or a Whitlow linker. In embodiments, the scFv is mROR-1 that has been humanized. In some embodiments, the scFv is hROR1(VH-VL)_14, hROR1(VL-VH)_05, hROR1(VH-VL)_14-3, hROR1(VH-VL)_14-4, hROR1(VH_5-VL_14), hROR1(VH_5-VL_16), hROR1(VH_18-VL_04), or hROR1(VH_18-VL_14). In some embodiments, the antigen binding moiety can comprise VH and VL that are directionally linked, for example, from N to C terminus, VH-linker-VL or VL-linker-VH. 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of amino acid sequences as shown in SEQ ID NOs: 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, and 74 (hROR1 VL). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of amino acid sequences as shown in SEQ ID NOs: 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, and 73 (hROR1 VH). 
     In embodiments, a CAR described herein comprises antigen binding moieties VL (SEQ ID NOs: 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, and 74) and VH (SEQ ID NOs: 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, and 73) with a Gly-Ser linker (SEQ ID NOs: 127, 129, or 130) or functional variants of the linker. 
     In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of amino acid sequences as shown in SEQ ID NOs: 3-14 and 75-82 (VH, VL and linker). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 15 (hROR1 VH_04). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 16 (hROR1 VL_04). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 17 (hROR1 VH_05). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 18 (hROR1 VL_05). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 19 (hROR1 VH_06). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 20 (hROR1 VL_06). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 21 (hROR1 VH_07). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 22 (hROR1 VL_07). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 23 (hROR1 VH_08). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 24 (hROR1 VL_08) 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 25 (hROR1 VH_09). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 26 (hROR1 VL_09). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 27 (hROR1 VH_10). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 28 (hROR1 VL_10). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 29 (hROR1 VH_11). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 30 (hROR1 VL_11). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 31 (hROR1 VH_12). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 32 (hROR1 VL_12). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 33 (hROR1 VH_13). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 34 (hROR1 VL_13). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 35 (hROR1 VH_14). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 36 (hROR1 VL_14). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 37 (hROR1 VH_14-1). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 38 (hROR1 VL_14-1). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 39 (hROR1 VH_14-2). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 40 (hROR1 VL_14-2). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 41 (hROR1 VH_14-3). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 42 (hROR1 VL_14-3). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 43 (hROR1 VH_14-4). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 44 (hROR1 VL_14-4). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 45 (hROR1 VH_14-5). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 46 (hROR1 VL_14-5). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 47 (hROR1 VH_15). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 48 (hROR1 VL_15). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 49 (hROR1 VH_16). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 50 (hROR1 VL_16). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 51 (hROR1 VH_17). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 52 (hROR1 VL_17). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 53 (hROR1 VH_18). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 54 (hROR1 VL_18). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 55 (hROR1 VH_19). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 56 (hROR1 VL_19). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 57 (hROR1 VH_20). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 58 (hROR1 VL_20). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 59 (hROR1 VH_21). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 60 (hROR1 VL_21). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 61 (hROR1 VH_22). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 62 (hROR1 VL_22). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 63 (hROR1 VH_23). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 64 (hROR1 VL_23). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 65 (hROR1 VH_24). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 66 (hROR1 VL_24). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 67 (hROR1 VH_25). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 68 (hROR1 VL_25). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 69 (hROR1 VH_26). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 70 (hROR1 VL_26). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 71 (hROR1 VH_27). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 72 (hROR1 VL_27). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 73 (hROR1 VH_28). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 74 (hROR1 VL_28). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having the amino acid sequence of SEQ ID NO: 17 (hROR1 VH_5) and a VL polypeptide having the amino acid sequence of SEQ ID NO: 18 (hROR1 VL_5). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having the amino acid sequence of SEQ ID NO: 35 (hROR1 VH_14) and a VL polypeptide having the amino acid sequence of SEQ ID NO: 36 (hROR1 VL_14). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having the amino acid sequence of SEQ ID NO: 41 (hROR1 VH_14-3) and a VL polypeptide having the amino acid sequence of SEQ ID NO: 42 (hROR1 VL_14-3). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having the amino acid sequence of SEQ ID NO: 43 (hROR1 VH_14-4) and a VL polypeptide having the amino acid sequence of SEQ ID NO: 44 (hROR1 VL_14-4). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having the amino acid sequence of SEQ ID NO: 17 (hROR1 VH_5) and a VL polypeptide having the amino acid sequence of SEQ ID NO: 36 (hROR1 VL_14). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having the amino acid sequence of SEQ ID NO: 53 (hROR1 VH_18) and a VL polypeptide having the amino acid sequence of SEQ ID NO: 16 (hROR1 VL_04). 
     In embodiments, a CAR described herein comprises an antigen-binding moiety comprising a VH polypeptide having the amino acid sequence of SEQ ID NO: 53 (hROR1 VH_18) and a VL polypeptide having the amino acid sequence of SEQ ID NO: 36 (hROR1 VL_14). 
     In embodiments, the antigen binding moiety has GM-CSFRa signal peptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 94. 
     In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 3. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 4. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 5. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 6. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 7. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 8. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 9. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 10. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 11. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 12. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 13. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 14. 
     In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 75. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 76. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 77. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 78. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 79. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 80. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 81. In embodiments, a CAR described herein comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 82. 
     Spacer 
     In embodiments, the ROR-1 CAR of the present disclosure comprises a spacer comprising one or more stalk regions and optionally one or more stalk extension regions, that provides a separation between the antigen binding moiety and the T cell membrane. In embodiments, the spacer establishes an optimal effector-target inter-membrane distance. In embodiments, the stalk domain provides flexibility for antigen binding domain to reach its target. In one embodiment, the stalk domain is a CD8alpha hinge domain. In some embodiments, the term “spacer,” “stalk regions” and “stalk domain” can be used interchangeably herein. 
     In embodiments, the CD8alpha hinge domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 88. 
     In other embodiments, between the extracellular domain and the transmembrane domain of the CAR, there is incorporated a spacer. As described herein, a spacer can comprise a stalk region and a stalk extension region as depicted in  FIG. 3  and  FIG. 4 . In one embodiment, a spacer can include a single stalk region. In another embodiment, a spacer can comprise a stalk region (designated as “5”) and stalk extension region(s), which is herein designated as “S′n.” For example, a spacer can comprise one (1) stalk region and S′n, wherein n can be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In one embodiment, when the scFv of the ROR1 CAR is mROR1 (SEQ ID NOs: 3-14) or hROR1 (SEQ ID NOs: 75-82), wherein n is not 0. 
     In further embodiments, the stalk region can be linked to stalk extension region S′n via a linker. A linker as described herein can include for instance, a GSG linker (SEQ ID NO: 129), SGSG linker (SEQ ID NO: 130), (G45)3 linker (SEQ ID NO: 127), (G45)4 linker (SEQ ID NO: 294) and/or a Whitlow linker (SEQ ID NO: 128). 
     In one embodiment, stalk region and stalk extension region(s) can be derived or designed from a polypeptide of natural or of synthetic origin. The stalk region and/or stalk extension region(s) can comprise hinge domain(s) derived from a cell surface protein or derivatives or variants thereof. In some embodiments, the stalk region and/or stalk extension region(s) can comprise a hinge domain derived from CD28 or CD8alpha (CD8a). In some embodiments, each of the stalk region and stalk extension region(s) can be derived from at least one of a CD8alpha hinge domain, a CD28 hinge domain, a CTLA-4 hinge domain, a LNGFR extracellular domain, IgG1 hinge, IgG4 hinge and CH2-CH3 domain. The stalk and stalk extension region(s) can be separately derived from any combination of CD8alpha hinge domain, CD28 hinge domain, CTLA-4 hinge domain, LNGFR extracellular domain, IgG1 hinge, IgG4 hinge or CH2-CH3 domain. As an example, the stalk region can be derived from CD8alpha hinge domain and at least one stalk extension region can be derived from CD28 hinge domain thus creating a hybrid spacer. As another example, the stalk region can be derived from an IgG1 hinge or IgG4 hinge and at least one stalk extension region can be derived from a CH2-CH3 domain of IgG. 
     In certain embodiments, the stalk region can comprise one or more dimerization sites to form homo or hetero dimerized chimeric polypeptides. In other embodiments, the stalk region or one or more stalk extension regions can contain mutations that eliminate dimerization sites altogether. In some embodiments, a stalk extension region(s) can contain at least one fewer dimerization site as compared to a stalk region. For example, if a stalk region comprises two dimerization sites, a stalk extension region can comprise one or zero dimerization sites. As another example, if a stalk region comprises one dimerization site, a stalk extension region can comprise zero dimerization sites. In some examples, the stalk extension region(s) lacks a dimerization site. 
     In some aspects of the embodiments disclosed herein, a stalk region of a subject antigen binding polypeptide comprises a sequence with at least about 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or greater identity to a CD8alpha hinge domain. A CD8alpha hinge domain can comprise a polypeptide sequence with at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or greater identity to the sequence shown in SEQ ID NO: 83. In some cases, a stalk extension region comprises a polypeptide sequence with at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, or greater identity to the sequence shown in SEQ ID NO: 83. In some cases, a stalk extension region comprises a nucleotide sequence with at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, or greater identity to the sequence shown in SEQ ID NO: 230. In some examples, a stalk region and stalk extension region can together comprise a polynucleotide sequence with at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, or greater identity to any one of the sequences shown in SEQ ID NOs: 230-233. 
     Transmembrane Domain 
     In embodiments, the CAR comprises a transmembrane domain that is fused to the extracellular domain of the CAR stalk domain. In one embodiment, the transmembrane domain that naturally is associated with one of the domains in the CAR is used. In embodiments, the transmembrane domain is a hydrophobic alpha helix that spans the membrane. 
     The transmembrane domain can be derived from either a natural or a synthetic source. Where the source is natural, the domain can be derived from any membrane-bound or transmembrane protein. Transmembrane regions of particular use in this invention can be derived from (i.e. comprise at least the transmembrane region(s) of) the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8alpha, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154. Alternatively the transmembrane domain can be synthetic, in which case it will comprise predominantly hydrophobic residues such as leucine and valine. In embodiments, a triplet of phenylalanine, tryptophan and valine will be found at each end of a synthetic transmembrane domain. Optionally, a short oligonucleotide or polypeptide linker, in embodiments, between 2 and 10 amino acids in length can form the linkage between the transmembrane domain and the cytoplasmic signaling domain of the CAR. In embodiments, the linker is a glycine-serine linker. 
     In embodiments, the transmembrane domain in a CAR described herein is the CD8alpha transmembrane domain. In embodiments, the CD8alpha transmembrane domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 87. 
     In embodiments, the transmembrane domain in a CAR described herein is the CD28 transmembrane domain. In embodiments, the CD28 transmembrane domain comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 88. 
     Cytoplasmic Domain (Co-Stimulatory Domain and Signaling Domain) 
     The cytoplasmic domain, also known as the intracellular signaling domain of a CAR described herein, is responsible for activation of at least one of the normal effector functions of the immune cell in which the CAR has been placed. The term “effector function” refers to a specialized function of a cell. Effector function of a T cell, for example, can be cytolytic activity or helper activity including the secretion of cytokines. Thus the term “intracellular signaling domain” refers to the portion of a protein which transduces the effector function signal and directs the cell to perform a specialized function. While usually the entire intracellular signaling domain can be employed, in many cases it is not necessary to use the entire chain. To the extent that a truncated portion of the intracellular signaling domain is used, such truncated portion can be used in place of the intact chain as long as it transduces the effector function signal. The term intracellular signaling domain is thus meant to include any truncated portion of the intracellular signaling domain sufficient to transduce the effector function signal. 
     Examples of intracellular signaling domains for use in a CAR described herein can include the cytoplasmic sequences of the T cell receptor (TCR) and co-receptors that act in concert to initiate signal transduction following antigen receptor engagement, as well as any derivative or variant of these sequences and any synthetic sequence that has the same functional capability. 
     Signals generated through the TCR alone are generally insufficient for full activation of the T cell and that a secondary or co-stimulatory signal is also required. Thus, T cell activation can be mediated by two distinct classes of cytoplasmic signaling sequence: those that initiate antigen-dependent primary activation through the TCR (primary cytoplasmic signaling sequences) and those that act in an antigen-independent manner to provide a secondary or co-stimulatory signal (secondary cytoplasmic signaling sequences). 
     Primary cytoplasmic signaling sequences regulate primary activation of the TCR complex either in a stimulatory way, or in an inhibitory way. Primary cytoplasmic signaling sequences that act in a stimulatory manner can contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs or ITAMs. 
     Examples of ITAM-containing primary cytoplasmic signaling sequences that are of particular use in the invention include those derived from TCR zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d. In embodiments, the cytoplasmic signaling molecule in a CAR described herein comprises a cytoplasmic signaling sequence derived from CD3 zeta. 
     In embodiments, the cytoplasmic domain of the CAR can be designed to comprise the CD3-zeta signaling domain by itself or combined with any other desired cytoplasmic domain(s) useful in the context of a CAR described herein. For example, the cytoplasmic domain of the CAR can comprise a CD3 zeta chain portion and a costimulatory signaling region. The costimulatory signaling region refers to a portion of the CAR comprising the intracellular domain of a costimulatory molecule. A costimulatory molecule is a cell surface molecule other than an antigen receptor or their ligands that is required for an efficient response of lymphocytes to an antigen. Examples of such molecules include CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, DAP10, DAP12 and a ligand that specifically binds with CD83, and the like. In embodiments, costimulatory molecules can be used together, e.g., CD28 and 4-1BB or CD28 and OX40. Thus, while the invention in exemplified primarily with 4-1BB and CD28 as the co-stimulatory signaling element, other costimulatory elements are within the scope of the invention. 
     The cytoplasmic signaling sequences within the cytoplasmic signaling portion of a CAR described herein can be linked to each other in a random or specified order. Optionally, a short oligo- or polypeptide linker, between 2 and 10 amino acids in length can form the linkage. A glycine-serine doublet provides a particularly suitable linker. 
     In one embodiment, the cytoplasmic domain comprises the signaling domain of CD3-zeta and the signaling domain of CD28. In another embodiment, the cytoplasmic domain comprises the signaling domain of CD3-zeta and the signaling domain of 4-1BB. In yet another embodiment, the cytoplasmic domain comprises the signaling domain of CD3-zeta and the signaling domains of CD28 and 4-1BB. 
     In one embodiment, the cytoplasmic domain in a CAR described herein comprises the signaling domain of 4-1BB and the signaling domain of CD3-zeta, wherein the signaling domain of 4-1BB comprises a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the polypeptide sequence of SEQ ID NO:89, and the signaling domain of CD3-zeta comprises a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the nucleic acid sequence of SEQ ID NO: 93. 
     In one embodiment, the cytoplasmic domain in a CAR described herein is designed to comprise the signaling domain of CD28 and the signaling domain of CD3-zeta, wherein the signaling domain of CD28 comprises a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the polypeptide sequence of SEQ ID NO: 90, and the signaling domain of CD3-zeta comprises a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the polypeptide sequence of SEQ ID NO: 93. 
     In one embodiment, the cytoplasmic domain in a CAR described herein is designed to comprise the signaling domain of DNAX-activation protein 10 (DAP10), wherein the signaling domain of DAP10 comprises a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the polypeptide sequence of SEQ ID NO: 91. 
     In one embodiment, the cytoplasmic domain in a CAR described herein is designed to comprise the signaling domain of DNAX-activation protein 12 (DAP12), wherein the signaling domain of DAP10 comprises a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the polypeptide sequence of SEQ ID NO: 92. 
     In one embodiment, the cytoplasmic domain in a CAR described herein comprises the signaling domain of 4-1BB and the signaling domain of CD3-zeta, wherein the signaling domain of 4-1BB comprises the amino acid sequence set forth in SEQ ID NO: 89 and the signaling domain of CD3-zeta comprises the amino acid sequence set forth in SEQ ID NO: 93. 
     Additional Genetic Elements 
     Although cellular therapies hold great promise for the treatment of human disease, significant toxicities from the cells themselves or from their transgene products have hampered clinical investigation. In embodiments described herein, immune effector cells comprising a CAR described herein that have been infused into a mammalian subject, e.g., a human, can be ablated in order to regulate the effect of such immune effector cells should toxicity arise from their use. Therefore, certain in embodiments, in addition to the therapeutic ROR-1-specific chimeric antigen receptor described herein, a second gene is also introduced into an engineered immune effector cell described herein. In some embodiments, the second gene is a “cell tag.” In some embodiments, the cell tag is a “kill switch.” In some embodiments, the second gene is effectively a “kill switch” that allows for the depletion of ROR-1 CAR or ROR-1 CAR/mblL-15 containing cells. In certain embodiments, the “kill switch” is a HER1 tag or a CD20 tag which comprise a HER1 polypeptide or a CD20 polypeptide which comprises at least an antibody binding epitope of HER1 or CD20 or functional fragment thereof, and optionally a signal polypeptide sequence or fragment thereof. 
     In certain embodiments, the second gene is a HER1 tag which is Epidermal Growth Factor Receptor (HER1) or a fragment or variant thereof. In embodiments, the second gene is a HER1 tag which is truncated human Epidermal Growth Factor Receptor 1 (for instance HER1t or HERM). In some cases, the second gene is a variant of a truncated human Epidermal Growth Factor Receptor 1. In embodiments, at least one of HER1, HER1t and HERM provides a safety mechanism by allowing for depletion of infused CAR-T cells through administering FDA approved cetuximab or any antibody that recognizes HER1, HER1t and/or HER1t1. In embodiments, the HER1t gene comprises a nucleotide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the nucleic acid sequence of SEQ ID NO: 256. In embodiments, the HERM gene comprises a nucleotide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the nucleic acid sequence of SEQ ID NO: 257. The truncated HER1 sequence, for instance HER1t and HERM eliminate the potential for EGF ligand binding, homo- and hetero-dimerization of EGFR, and EGFR mediated signaling while keeping cetuximab binding to the receptor intact (Ferguson, K., 2008. A structure-based view of Epidermal Growth Factor Receptor regulation.  Annu Rev Biophys , Volume 37, pp. 353-373). 
     In some embodiments, the HER1t tag has a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the sequence of SEQ ID NO: 109. In some embodiments, the HERM tag has a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the sequence of SEQ ID NO: 110. 
     In further embodiments, in addition to the therapeutic ROR-1-specific chimeric antigen receptor of the invention the second gene introduced is a CD20 tag. In some cases, the CD20 tag is a full-length CD20 polypeptide, or a truncated CD20 polypeptide (CD20t-1). In some cases, the CD20 tag, for instance CD20 or CD20t-1 also provides a safety mechanism by allowing for depletion of infused CAR-T cells through administering FDA-approved rituximab therapy. In certain embodiments, the CD20 tag has a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the sequence of SEQ ID NO: 111. In certain embodiments, the CD20 tag is a CD20t-1 tag and has a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the sequence of SEQ ID NO: 112. In some embodiments, the CD20 tag is encoded by a CD20 gene which comprises a nucleotide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the nucleic acid sequence of SEQ ID NO: 258. In some embodiments, the CD20 tag is encoded by a CD20t-1 gene which comprises a nucleotide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the nucleic acid sequence of SEQ ID NO: 259. 
     In embodiments, a CAR vector comprising a CAR described herein further comprises a full length CD20 tag comprising a nucleic acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the nucleic acid sequence of SEQ ID NO: 258. 
     In embodiments, the gene encoding the kill tag, for instance the HERR, HER1t-1, CD20 or CD20t-1 tag, is genetically fused to the ROR-1 CAR at 3′ end via in-frame with a self-cleaving peptide, for example but not restricted to Thosea asigna virus (T2A) peptide. In embodiments, the T2A peptide has an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 116. 
     In embodiments, the kill tag gene is cloned into a lentiviral plasmid backbone in frame with the ROR-1 CAR gene. In other embodiments, the kill tag is cloned into a separate lentiviral vector. In other embodiments, both genes are cloned into a Sleeping Beauty transposon vector. In yet other embodiments, the kill tag such as HERR, HER1t-1, CD20 or CD20t-1 is cloned into a separate Sleeping Beauty transposon vector. In certain embodiments, the kill tags have a signal peptide, for instance, GM-CSFRa signal peptide wherein the GM-CSFRa signal peptide has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 94. In certain embodiments, the signal peptide is IgK having a sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the nucleic acid sequence of SEQ ID NO: 95. 
     In one embodiment, the signal peptide is Mouse Ig VH region 3 (SEQ ID NO: 101), Azurocidin (SEQ ID NO: 103), IGHV3-23 (SEQ ID NO: 106), IGKV1-D33 (HuL1) (SEQ ID NO: 107) or IGKV1-D33 (L14F) (HuH7) (SEQ ID NO: 108). 
     Exemplary gene expression cassettes encoding a CAR and a kill tag as described herein are shown in  FIG. 1  and  FIG. 2 . 
     Exemplary CAR Open Reading Frames 
     Exemplary CAR and human ROR-1 receptor open reading frames encompassed by methods and compositions described herein are in Table 1: 
     
       
         
           
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 SEQ 
                   
               
               
                 ID NO 
                 CAR ORF 
               
               
                   
               
             
            
               
                 75 
                 hROR1(VH-VL)_14.CD8a(3x).CD28z 
               
               
                 76 
                 hROR1(VL-VH)_05.CD8a(3x).CD28z 
               
               
                 77 
                 hROR1(VH-VL)_14-3.CD8a(3x).CD28z 
               
               
                 78 
                 hROR1(VH-VL)_14-4.CD8a(3x).CD28z 
               
               
                 79 
                 hROR1(VH_5-VL_14).CD8a(3x).CD28z 
               
               
                 80 
                 hROR1(VH_5-VL_16).CD8a(3x).CD28z 
               
               
                 82 
                 hROR1(VH_18-VL_04).CD8a(3x).CD28z 
               
               
                 82 
                 hROR1(VH_18-VL_14).CD8a(3x).CD28z 
               
               
                   
               
            
           
         
       
     
     In embodiments, provided herein is an isolated nucleic acid encoding a CAR, wherein the CAR comprises a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with an amino acid of SEQ ID NOs: 3-14 or SEQ ID NOs: 75-82. 
     In embodiments, the CAR hROR1(VH-VL)_14.CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 17 (hROR1 VH_5) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 18 (hROR1 VL_5). 
     In embodiments, the CAR hROR1(VL-VH)_05.CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 35 (hROR1 VH_14) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 36 (hROR1 VL_14). 
     In embodiments, the CAR hROR1(VH-VL)_14-3.CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 41 (hROR1 VH_14-3) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 42 (hROR1 VL_14-3). 
     In embodiments, the CAR hROR1(VH-VL)_14-4.CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 43 (hROR1 VH_14-4) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 44 (hROR1 VL_14-4). 
     In embodiments, the CAR hROR1(VH_5-VL_14).CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 17 (hROR1 VH_5) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 36 (hROR1 VL_14). 
     In embodiments, the CAR hROR1(VH_5-VL_16).CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 17 (hROR1 VH_05) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 50 (hROR1 VL_16). 
     In embodiments, the CAR hROR1(VH_18-VL_04).CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 53 (hROR1 VH_18) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 16 (hROR1 VL_04). 
     In embodiments, the CAR hROR1(VH_18-VL_14).CD8a(3×).CD28z comprises an antigen-binding moiety comprising a VH polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 53 (hROR1 VH_18) and a VL polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 36 (hROR1 VL_14). 
     In each of the embodiments in Table 1, the signal peptide of the CAR can comprise a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of Mouse Ig VH region 3 (SEQ ID NO: 101), Azurocidin (SEQ ID NO: 103), IGHV3-23 (SEQ ID NO: 106), IGKV1-D33 (HuL1) (SEQ ID NO: 107) or IGKV1-D33 (L14F) (HuH7) (SEQ ID NO: 108). 
     In each of the embodiments in Table 1 with “CD8a,” the transmembrane region of the CAR comprises CD8alpha transmembrane domain comprising a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 87, and the spacer is CD8a comprising a polypeptide having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of the amino acid sequences as shown in SEQ ID NOs: 83-86. 
     In each of the embodiments in Table 1 with “CD28m,” the intracellular domain of the CAR comprises CD28 with an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 90. 
     In each of the embodiments in Table 1 with “T2A”, the CAR ORF comprises a self-cleaving Thosea asigna virus (T2A) peptide, which enables the production of multiple gene products from a single vector. In embodiments, the T2A peptide has an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 116. 
     In the embodiments in Table 1 with “HER1t,” the CAR ORF comprises truncated human Epidermal Growth Factor Receptor 1 (HER1t), which provides a safety mechanism by allowing for depletion of infused CAR-T cells through administering FDA approved cetuximab therapy. The HER1t gene as described herein can comprise a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 109. Unless otherwise noted in Table 1, HER1t tags have GM-CSFRa signal peptide (“GM-CSFRsp”) (SEQ ID NO: 94). In one embodiment, the signal peptide is Mouse Ig VH region 3 (SEQ ID NO: 101), Azurocidin (SEQ ID NO: 103), IGHV3-23 (SEQ ID NO: 106), IGKV1-D33 (HuL1) (SEQ ID NO: 107) or IGKV1-D33 (L14F) (HuH7) (SEQ ID NO: 108). In certain embodiments, the HER1t can be substituted with another tag, for instance, HER1t-1. The HER1t-1 gene as described herein can comprise a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 110. In the embodiments in Table 1 with “IgKsp,” the signal peptide is IgK having an amino acid sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 95. 
     In embodiments in Table 1 with “4-1BB,” the CAR ORF comprises costimulatory molecule having a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 89. 
     In embodiments in Table 1 with “FL CD20,” the CAR ORF comprises a full length CD20 tag comprising a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 111. CD20 provides a safety mechanism by allowing for depletion of infused CAR-T cells through administering FDA-approved rituximab therapy. In other embodiments, FL CD20 can be substituted with CD20t-1 comprising a polypeptide sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 112. 
     In certain embodiments in Table 1, the CAR ORF can be under the control of an inducible promoter for gene transcription. In one aspect, the inducible promoter can be a gene switch ligand inducible promoter. In some cases, an inducible promoter can be a small molecule ligand-inducible two polypeptide ecdysone receptor-based gene switch, such as RHEOSWITCH® gene switch. In some embodiments, the CAR ORF and gene switch components can be configured as depicted in  FIGS. 1A-1E  and  FIGS. 2A-2E . 
     Cytokines 
     In some embodiments, a CAR described herein is administered to a subject with one or more additional therapeutic agents that include but are not limited to cytokines. In some cases, the cytokine comprises at least one chemokine, interferon, interleukin, lymphokine, tumor necrosis factor, or variant or combination thereof. In some cases, the cytokine is an interleukin. In some cases the interleukin is at least one of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33 and functional variants and fragments thereof. In some embodiments, the cytokines can be membrane bound or secreted. In embodiments, the cytokine is soluble IL-15, soluble IL-15/IL-15Ra complex (e.g., ALT-803). In certain cases, the interleukin can comprise membrane bound IL-15 (mbIL-15) or a fusion of IL-15 and IL-15Ra. In some embodiments, a mbIL-15 is a membrane-bound chimeric IL-15 which can be co-expressed with a modified immune effector cell described herein. In some embodiments, the mbIL-15 comprises a full-length IL-15 (e.g., a native IL-15 polypeptide) or fragment or variant thereof, fused in frame with a full length IL-15Ra, functional fragment or variant thereof. In some cases, the IL-15 is indirectly linked to the IL-15Ra through a linker. In some instances, the mbIL-15 is as described in Murton et al., “Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells,” PNAS 2016. In some cases, the cytokine is expressed in the same immune effector cell as the CAR. 
     In further embodiments, an immune effector cell expressing a CAR described herein expresses membrane-bound IL-15 (“mIL-15 or mbIL-15”). In aspects of the invention, the mbIL-15 comprises a fusion protein between IL-15 and IL-15Rα. In further embodiments, the mbIL-15 comprises an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with the amino acid sequence of SEQ ID NO: 113. In certain cases, the CAR and the cytokine is expressed in separate vectors. In specific cases, the vectors can be lentiviral vectors, retroviral vectors or Sleeping Beauty transposons. 
     In some embodiments, the mbIL-15 is expressed with a cell tag such as HERR, HER-1t-1, CD20t-1 or CD20 as described herein. The mbIL-15 can be expressed in-frame with HERR, HER-1t-1, CD20t-1 or CD20. 
     In some embodiments, the mbIL-15 can be under the control of an inducible promoter for gene transcription. In one aspect, the inducible promoter can be a gene switch ligand inducible promoter. In some cases, an inducible promoter can be a small molecule ligand-inducible two polypeptide ecdysone receptor-based gene switch, such as RHEOSWITCH® gene switch. 
     In another aspect, the interleukin can comprise IL-12. In some embodiments, the IL-12 is a single chain IL-12 (scIL-12), protease sensitive IL-12, destabilized IL-12, membrane bound IL-12, intercalated IL-12. In some instances, the IL-12 variants are as described in WO2015/095249, WO2016/048903, WO2017/062953, all of which is incorporated by reference in their entireties. 
     In some embodiments, the cytokines described above can be under the control of an inducible promoter for gene transcription. In one aspect, the inducible promoter can be a gene switch ligand inducible promoter. In some cases, an inducible promoter can be a small molecule ligand-inducible two polypeptide ecdysone receptor-based gene switch, such as RHEOSWITCH® gene switch. 
     Gene Switch 
     Provided herein are gene switch polypeptides, polynucleotides encoding ligand-inducible gene switch polypeptides, and methods and systems incorporating these polypeptides and/or polynucleotides. The term “gene switch” refers to the combination of a response element associated with a promoter, and for instance, an ecdysone receptor (EcR) based system which, in the presence of one or more ligands, modulates the expression of a gene into which the response element and promoter are incorporated. Tightly regulated inducible gene expression systems or gene switches are useful for various applications such as gene therapy, large scale production of proteins in cells, cell based high throughput screening assays, functional genomics and regulation of traits in transgenic plants and animals. Such inducible gene expression systems can include ligand inducible heterologous gene expression systems. 
     An early version of EcR-based gene switch used  Drosophila melanogaster  EcR (DmEcR) and  Mus musculus  RXR (MmRXR) polypeptides and showed that these receptors in the presence of steroid, ponasteroneA, transactivate reporter genes in mammalian cell lines and transgenic mice (Christopherson et al., 1992; No et al., 1996). Later, Suhr et al., 1998 showed that non-steroidal ecdysone agonist, tebufenozide, induced high level of transactivation of reporter genes in mammalian cells through  Bombyx mori  EcR (BmEcR) in the absence of exogenous heterodimer partner. 
     International Patent Applications No. PCT/US97/05330 (WO 97/38117) and PCT/US99/08381 (WO99/58155) disclose methods for modulating the expression of an exogenous gene in which a DNA construct comprising the exogenous gene and an ecdysone response element is activated by a second DNA construct comprising an ecdysone receptor that, in the presence of a ligand therefor, and optionally in the presence of a receptor capable of acting as a silent partner, binds to the ecdysone response element to induce gene expression. In this example, the ecdysone receptor was isolated from  Drosophila melanogaster . Typically, such systems require the presence of the silent partner, preferably retinoid X receptor (RXR), in order to provide optimum activation. In mammalian cells, insect ecdysone receptor (EcR) is capable of heterodimerizing with mammalian retinoid X receptor (RXR) and, thereby, be used to regulate expression of target genes or heterologous genes in a ligand dependent manner. International Patent Application No. PCT/US98/14215 (WO 99/02683) discloses that the ecdysone receptor isolated from the silk moth  Bombyx mori  is functional in mammalian systems without the need for an exogenous dimer partner. 
     U.S. Pat. No. 6,265,173 discloses that various members of the steroid/thyroid superfamily of receptors can combine with  Drosophila melanogaster  ultraspiracle receptor (USP) or fragments thereof comprising at least the dimerization domain of USP for use in a gene expression system. U.S. Pat. No. 5,880,333 discloses a  Drosophila melanogaster  EcR and ultraspiracle (USP) heterodimer system used in plants in which the transactivation domain and the DNA binding domain are positioned on two different hybrid proteins. In each of these cases, the transactivation domain and the DNA binding domain (either as native EcR as in International Patent Application No. PCT/US98/14215 or as modified EcR as in International Patent Application No. PCT/US97/05330) were incorporated into a single molecule and the other heterodimeric partners, either USP or RXR, were used in their native state. 
     International Patent Application No. PCT/US01/0905 discloses an ecdysone receptor-based inducible gene expression system in which the transactivation and DNA binding domains are separated from each other by placing them on two different proteins results in greatly reduced background activity in the absence of a ligand and significantly increased activity over background in the presence of a ligand. This two-hybrid system is a significantly improved inducible gene expression modulation system compared to the two systems disclosed in applications PCT/US97/05330 and PCT/US98/14215. The two-hybrid system is believed to exploit the ability of a pair of interacting proteins to bring the transcription activation domain into a more favorable position relative to the DNA binding domain such that when the DNA binding domain binds to the DNA binding site on the gene, the transactivation domain more effectively activates the promoter (see, for example, U.S. Pat. No. 5,283,173). The two-hybrid gene expression system comprises two gene expression cassettes; the first encoding a DNA binding domain fused to a nuclear receptor polypeptide, and the second encoding a transactivation domain fused to a different nuclear receptor polypeptide. In the presence of ligand, it is believed that a conformational change is induced which promotes interaction of the first polypeptide with the second polypeptide thereby resulting in dimerization of the DNA binding domain and the transactivation domain. Since the DNA binding and transactivation domains reside on two different molecules, the background activity in the absence of ligand is greatly reduced. 
     Certain modifications of the two-hybrid system could also provide improved sensitivity to non-steroidal ligands for example, diacylhydrazines, when compared to steroidal ligands for example, ponasterone A (“PonA”) or muristerone A (“MurA”). That is, when compared to steroids, the non-steroidal ligands provided higher gene transcription activity at a lower ligand concentration. Furthermore, the two-hybrid system avoids some side effects due to overexpression of RXR that can occur when unmodified RXR is used as a switching partner. In a preferred two-hybrid system, native DNA binding and transactivation domains of EcR or RXR are eliminated and as a result, these hybrid molecules have less chance of interacting with other steroid hormone receptors present in the cell, thereby resulting in reduced side effects. 
     The ecdysone receptor (EcR) is a member of the nuclear receptor superfamily and is classified into subfamily 1, group H (referred to herein as “Group H nuclear receptors”). The members of each group share 40-60% amino acid identity in the E (ligand binding) domain (Laudet et al., A Unified Nomenclature System for the Nuclear Receptor Subfamily, 1999; Cell 97: 161-163). In addition to the ecdysone receptor, other members of this nuclear receptor subfamily 1, group H include: ubiquitous receptor (UR), Orphan receptor 1 (OR-1), steroid hormone nuclear receptor 1 (NER-1), RXR interacting protein-15 (RIP-15), liver x receptor (3 (LXR(3), steroid hormone receptor like protein (RLD-1), liver x receptor (LXR), liver x receptor α (LXRα), farnesoid x receptor (FXR), receptor interacting protein 14 (RIP-14), and farnesol receptor (HRR-1). 
     In some cases, an inducible promoter (“IP”) can be a small molecule ligand-inducible two polypeptide ecdysone receptor-based gene switch, such as Intrexon Corporation&#39;s RHEOSWITCH® gene switch. In some cases, a gene switch can be selected from ecdysone-based receptor components as described in, but without limitation to, any of the systems described in: PCT/US2001/009050 (WO 2001/070816); U.S. Pat. Nos. 7,091,038; 7,776,587; 7,807,417; 8,202,718; PCT/US2001/030608 (WO 2002/029075); U.S. Pat. Nos. 8,105,825; 8,168,426; PCT/1152002/005235 (WO 2002/066613); U.S. application Ser. No. 10/468,200 (U.S. Pub. No. 20120167239); PCT/US2002/005706 (WO 2002/066614); U.S. Pat. Nos. 7,531,326; 8,236,556; 8,598,409; PCT/US2002/005090 (WO 2002/066612); U.S. Pat. No. 8,715,959 (U.S. Pub. No. 20060100416); PCT/US2002/005234 (WO 2003/027266); U.S. Pat. Nos. 7,601,508; 7,829,676; 7,919,269; 8,030,067; PCT/US2002/005708 (WO 2002/066615); U.S. application Ser. No. 10/468,192 (U.S. Pub. No. 20110212528); PCT/US2002/005026 (WO 2003/027289); U.S. Pat. Nos. 7,563,879; 8,021,878; 8,497,093; PCT/US2005/015089 (WO 2005/108617); U.S. Pat. Nos. 7,935,510; 8,076,454; PCT/US2008/011270 (WO 2009/045370); U.S. application Ser. No. 12/241,018 (U.S. Pub. No. 20090136465); PCT/US2008/011563 (WO 2009/048560); U.S. application Ser. No. 12/247,738 (U.S. Pub. No. 20090123441); PCT/US2009/005510 (WO 2010/042189); U.S. application Ser. No. 13/123,129 (U.S. Pub. No. 20110268766); PCT/US2011/029682 (WO 2011/119773); U.S. application Ser. No. 13/636,473 (U.S. Pub. No. 20130195800); PCT/US2012/027515 (WO 2012/122025); and, U.S. Pat. No. 9,402,919; each of which is incorporated by reference in its entirety. 
     Provided are systems for modulating the expression of a CAR and/or a cytokine in a host cell, comprising polynucelotides encoding for gene-switch polypeptides disclosed herein. Further provided herein are polynucleotides encoding gene switch polypeptides for ligand-inducible control of gene expression, wherein the gene switch polypeptides comprise (a) a first gene switch polypeptide comprising a DNA-binding domain (DBD) fused to a nuclear receptor ligand binding domain; and (b) a second gene switch polypeptide comprising a transactivation domain fused to a nuclear receptor ligand binding domain; wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. In some embodiments, the linker is a cleavable or ribosome skipping linker sequence selected from the group consisting of 2A, GSG-2A, GSG linker (SEQ ID NO: 129), SGSG linker (SEQ ID NO: 130), furinlink variants and derivatives thereof. In certain embodiments, the 2A linker is a p2A linker, a T2A linker, F2A linker, or E2A linker. 
     In some embodiments, the DNA binding domain (DBD) comprises at least one of GAL4 (GAL4 DBD), a LexA DBD, a transcription factor DBD, a steroid/thyroid hormone nuclear receptor superfamily member DBD, a bacterial LacZ DBD, and a yeast DBD. In some cases, the transactivation domain comprises at least one of a VP16 transactivation domain, and a B42 acidic activator transactivation domain. In other cases, the nuclear receptor ligand binding domain comprises at least one of a ecdysone receptor (EcR), a ubiquitous receptor, an orphan receptor 1, a NER-1, a steroid hormone nuclear receptor 1, a retinoid X receptor interacting protein-15, a liver X receptor β, a steroid hormone receptor like protein, a liver X receptor, a liver X receptor α, a farnesoid X receptor, a receptor interacting protein 14, and a famesol receptor. In some embodiments, the nuclear receptor ligand binding domain is derived from the Ecdysone Receptor polypeptide sequence of SEQ ID NOs: 135 and 136. 
     In yet another embodiment, the first gene switch polypeptide comprises a GAL4 DBD fused to an EcR nuclear receptor ligand binding domain, and the second gene switch polypeptide comprises a VP16 transactivation domain fused to a retinoid receptor X (RXR) nuclear receptor ligand binding domain. In some cases, the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker, which is selected from the group consisting of 2A, GSG-2A, GSG linker (SEQ ID NO: 129), SGSG linker (SEQ ID NO: 130), furinlink variants and derivatives thereof. 
     In certain embodiments, two or more polypeptides encoded by a polynucleotide described herein can be separated by an intervening sequence encoding a linker polypeptide. In certain cases, the linker is a cleavage-susceptible linker. In some embodiments, polypeptides of interest are expressed as fusion proteins linked by a cleavage-susceptible linker polypeptide. In certain embodiments, cleavage-susceptible linker polypeptide(s) can be any one or more of: F/T2A, T2A, p2A, 2A, GSG-p2A, GSG linker (SEQ ID NO: 129), and furinlink variants. In certain embodiments, the linker polypeptide comprises any one of the amino acid sequences as shown in SEQ ID NOs: 116-130. 
     In some cases, a viral 2A sequence can be used. 2A elements can be shorter than IRES, having from 5 to 100 base pairs. In some cases, a 2A sequence can have 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 100 nucleotides in length. 2A linked genes can be expressed in one single open reading frame and “self-cleavage” can occur co-translationally between the last two amino acids, GP, at the C-terminus of the 2A polypeptide, giving rise to equal amounts of co-expressed proteins. 
     A viral 2A sequence can be about 20 amino acids. In some cases, a viral 2A sequence can contain a consensus motif Asp-Val/Ile-Glu-X-Asn-Pro-Gly-Pro (SEQ ID NO: 286). A consensus motif sequence can act co-translationally. For example, formation of a normal peptide bond between a glycine and proline residue can be prevented, which can result in ribosomal skipping and cleavage of a nascent polypeptide. This effect can produce multiple genes at equimolar levels. 
     A 2A peptide can allow translation of multiple proteins in a single open reading frame into a polypeptide that can be subsequently cleaved into individual polypeptide through a ribosome-skipping mechanism (Funston, Kallioinen et al. 2008). In some embodiments, a 2A sequence can include: F/T2A, T2A, p2A, 2A, T2A, E2A, F2A, and BmCPV2A, BmIFV2A, and any combination thereof. 
     In some cases, a vector can comprise an IRES sequence and a 2A linker sequence. In other cases, expression of multiple genes linked with 2A peptides can be facilitated by a spacer sequence (GSG (SEQ ID NO: 129)) ahead of the 2A peptides. In some cases, constructs can combine a spacers, linkers, adaptors, promotors, or combinations thereof. For example, a construct can have a spacer (SGSG (SEQ ID NO: 130) or GSG (SEQ ID NO: 129)) and furin linker (R-A-K-R (SEQ ID NO: 125)) cleavage site with different 2A peptides. A spacer can be an I-Ceui. In some cases, a linker can be engineered. For example, a linker can be designed to comprise chemical characteristics such as hydrophobicity. In some cases, at least two linker sequences can produce the same protein. In other cases, multiple linkers can be used in a vector. For example, genes of interest can be separated by at least two linkers. 
     In certain embodiments, two or more polypeptides encoded by a polynucleotide described herein can be separated by an intervening sequence encoding a linker polypeptide. In certain cases, the linker is a cleavage-susceptible linker. In some embodiments, polypeptides of interest are expressed as fusion proteins linked by a cleavage-susceptible linker polypeptide. In certain embodiments, cleavage-susceptible linker polypeptide(s) can be any one or two of: Furinlink, fmdv, p2a, GSG-p2a, and/or fp2a described in SEQ ID NOs: 119, 120, 121, 125, and 128. 
     In some embodiments, a linker can be utilized in a polynucleotide described herein. A linker can be a flexible linker, a rigid linker, an in vivo cleavable linker, or any combination thereof. In some cases, a linker can link functional domains together (as in flexible and rigid linkers) or releasing free functional domain in vivo as in in vivo cleavable linkers. 
     Linkers can improve biological activity, increase expression yield, and achieving desirable pharmacokinetic profiles. A linker can also comprise hydrazone, peptide, disulfide, or thioesther. 
     In some cases, a linker sequence described herein can include a flexible linker. Flexible linkers can be applied when a joined domain requires a certain degree of movement or interaction. Flexible linkers can be composed of small, non-polar (e.g., Gly) or polar (e.g., Ser or Thr) amino acids. A flexible linker can have sequences consisting primarily of stretches of Gly and Ser residues (“GS” linker). An example of a flexible linker can have the sequence of (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 287). By adjusting the copy number “n”, the length of this exemplary GS linker can be optimized to achieve appropriate separation of functional domains, or to maintain necessary inter-domain interactions. For example, (Gly-Gly-Gly-Gly-Ser)n, wherein n is 3 is (G45)3 linker as shown in SEQ ID NO: 127. Besides GS linkers, other flexible linkers can be utilized for recombinant fusion proteins. In some cases, flexible linkers can also be rich in small or polar amino acids such as Gly and Ser, but can contain additional amino acids such as Thr and Ala to maintain flexibility. In other cases, polar amino acids such as Lys and Glu can be used to improve solubility. 
     Flexible linkers included in linker sequences described herein, can be rich in small or polar amino acids such as Gly and Ser to provide good flexibility and solubility. Flexible linkers can be suitable choices when certain movements or interactions are desired for fusion protein domains. In addition, although flexible linkers do not have rigid structures in some cases, they can serve as a passive linker to keep a distance between functional domains. The length of a flexible linkers can be adjusted to allow for proper folding or to achieve optimal biological activity of the fusion proteins. 
     A linker described herein can further include a rigid linker in some cases. A rigid linker can be utilized to maintain a fixed distance between domains of a polypeptide. Examples of rigid linkers can be: Alpha helix-forming linkers, Pro-rich sequence, (XP)n, X-Pro backbone, A(EAAAK)nA (n=2-5) (SEQ ID NO: 288), to name a few. Rigid linkers can exhibit relatively stiff structures by adopting a-helical structures or by containing multiple Pro residues in some cases. 
     A linker described herein can be cleavable in some cases. In other cases a linker is not cleavable. Linkers that are not cleavable can covalently join functional domains together to act as one molecule throughout an in vivo processes or an ex vivo process. A linker can also be cleavable in vivo. A cleavable linker can be introduced to release free functional domains in vivo. A cleavable linker can be cleaved by the presence of reducing reagents, proteases, to name a few. For example, a reduction of a disulfide bond can be utilized to produce a cleavable linker. In the case of a disulfide linker, a cleavage event through disulfide exchange with a thiol, such as glutathione, could produce a cleavage. In other cases, an in vivo cleavage of a linker in a recombinant fusion protein can also be carried out by proteases that can be expressed in vivo under pathological conditions (e.g., cancer or inflammation), in specific cells or tissues, or constrained within certain cellular compartments. In some cases, a cleavable linker can allow for targeted cleavage. For example, the specificity of many proteases can offer slower cleavage of a linker in constrained compartments. A cleavable linker can also comprise hydrazone, peptides, disulfide, or thioesther. For example, a hydrazone can confer serum stability. In other cases, a hydrazone can allow for cleavage in an acidic compartment. An acidic compartment can have a pH up to 7. A linker can also include a thioether. A thioether can be nonreducible A thioether can be designed for intracellular proteolytic degradation. 
     In certain embodiments, an fmdv linker polypeptide comprises a sequence that can be at least about 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 126. In certain embodiments, an fmdv linker polypeptide is one or more of the linkers encoded in a single vector linking two or more fusion proteins. In certain cases, an fmdv linker polypeptide can be encoded by a polynucleotide open reading frame (ORF) nucleic acid sequence. In some cases, an ORF encoding fmdv comprises or consists of a sequence of SEQ ID NO: 272. In certain embodiments, a polynucleotide encoding fmdv is at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 272. 
     In certain cases, a linker polypeptide can be a “p2a” linker. In certain embodiments, a p2a polypeptide can comprise a sequence that can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 119. In certain embodiments, the p2a linker polypeptide can be one or more of the linkers encoded in a single vector linking two or more fusion proteins. In some cases, a p2a linker polypeptide can be encoded by a polynucleotide open reading frame (ORF) nucleic acid sequence. In certain embodiments, an ORF encoding p2a comprises or consists of the sequence of SEQ ID NO: 266. In certain cases, a polynucleotide encoding p2a can be or can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 266. 
     In some cases, a linker polypeptide can be a “GSG-p2a” linker. In certain embodiments, a GSG-p2a linker polypeptide can comprise a sequence that can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 120. In certain embodiments, a GSG-p2a linker polypeptide can be one or more of the linkers encoded in a single vector linking two or more fusion proteins. In some cases, a GSG-p2a linker polypeptide can be encoded by a polynucleotide open-reading frame (ORF) nucleic acid sequence. An ORF encoding GSG p2a can comprises the sequence of SEQ ID NO: 267. In some cases, a polynucleotide encoding GSG-p2a can be or can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 267. 
     A linker polypeptide can be an “fp2a” linker as provided herein. In certain embodiments, a fp2a linker polypeptide can comprise a sequence that can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 121. In certain cases, an fp2a linker polypeptide can be one or more of the linkers encoded in a single vector linking two or more fusion proteins. In some cases, a fp2a linker polypeptide can be encoded by a polynucleotide open reading frame (ORF) nucleic acid sequence. In certain embodiments, a polynucleotide encoding an fp2a linker can be or can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 268. 
     In some cases, a linker can be engineered. For example, a linker can be designed to comprise chemical characteristics such as hydrophobicity. In some cases, at least two linker sequences can produce the same protein. A sequence can be or can be about 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to a sequence of SEQ ID NO: 116 to SEQ ID NO: 130. In other cases, multiple linkers can be used in a vector. For example, genes of interest, and one or more gene switch polypeptide sequences described herein can be separated by at least two linkers. In some cases, genes can be separated by 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 linkers. 
     A linker can be an engineered linker. Methods of designing linkers can be computational. In some cases, computational methods can include graphic techniques. Computation methods can be used to search for suitable peptides from libraries of three-dimensional peptide structures derived from databases. For example, a Brookhaven Protein Data Bank (PDB) can be used to span the distance in space between selected amino acids of a linker. 
     In some embodiments are polynucleotides encoding a polypeptide construct comprising a furin polypeptide and a 2A polypeptide, wherein the furin polypeptide and the 2A polypeptide are connected by a polypeptide linker comprising at least three hydrophobic amino acids. In some cases, at least three hydrophobic amino acids are selected from the list consisting of glycine (Gly)(G), alanine (Ala)(A), valine (Val)(V), leucine (Leu)(L), isoleucine (Ile)(I), proline (Pro)(P), phenylalanine (Phe)(F), methionine (Met)(M), tryptophan (Trp)(W). In some cases, a polypeptide linker can also include one or more GS linker sequences, for instance (GS)n (SEQ ID NO: 289), (SG)n (SEQ ID NO: 290), (GSG)n (SEQ ID NO: 291) and (SGSG)n (SEQ ID NO: 292) wherein n can be any number from zero to fifteen. 
     Provided are methods of obtaining an improved expression of a polypeptide construct comprising: providing a polynucleotide encoding said polypeptide construct comprising a first functional polypeptide and a second functional polypeptide, wherein said first functional polypeptide and second functional polypeptide are connected by a linker polypeptide comprising a sequence with at least 60% identity to the sequence APVKQ (SEQ ID NO: 293); and expressing said polynucleotide in a host cell, wherein said expressing results in an improved expression of the polypeptide construct as compared to a corresponding polypeptide construct that does not have a linker polypeptide comprising a sequence with at least 60% identity to the sequence APVKQ (SEQ ID NO: 293). 
     In other instances, the linker can be an IRES. The term “internal ribosome entry site (IRES)” as used herein can be intended to mean internal ribosomal entry site. In a vector comprising an IRES sequence, a first gene can be translated by a cap-dependent, ribosome scanning, mechanism with its own 5′-UTR, whereas translation of a subsequent gene can be accomplished by direct recruitment of a ribosome to an IRES in a cap-independent manner. An IRES sequence can allow eukaryotic ribosomes to bind and begin translation without binding to a 5′ capped end. An IRES sequence can allow expression of multiple genes from one transcript (Mountford and Smith 1995). 
     Exemplary IRES sequences can be found in SEQ ID NO: 146 and 147. In certain cases, a polynucleotide encoding 2×Rbm3 IRES a can be or can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 146. In certain cases, a polynucleotide encoding EMCV IRES a can be or can be about at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% identical to SEQ ID NO: 147. 
     In some embodiments are systems for modulating the expression of a CAR and a cytokine in a host cell, comprising a first gene expression cassette comprising a first polynucleotide encoding a first polypeptide; a second gene expression cassette comprising a second polynucleotide encoding a second polypeptide; and a ligand; wherein the first and second polypeptides comprise one or more of: (i) a transactivation domain; (ii) a DNA-binding domain; and (iii) a ligand binding domain; (iv) CAR; (vi) cytokine, and/or (vii) cell tag such that upon contacting the host cell with the first gene expression cassette and the second gene expression cassette in the presence of the ligand, the CAR and the cytokine are expressed in the host cell. In some cases, the CAR is a ROR-1 CAR and the cytokine is mbIL-15. In some cases, ROR-1CAR, mbIL-15 are co-expressed with one cell tag. In some cases, ROR-1 CAR and mbIL-15 are each co-expressed with a cell tag. In other cases, ROR-1 CAR is expressed with a cell tag and mbIL-15 is expressed with a second cell tag. Exemplary configurations of gene expression cassettes are depicted in  FIGS. 1 and 2 . In other cases, the CAR is a ROR-1 CAR and the cytokine is IL-12. In some cases, ROR-1 CAR, IL-12 are co-expressed with one cell tag. In some cases, ROR-1 CAR and IL-12 are each co-expressed with a cell tag. In other cases, ROR-1 CAR is expressed with a cell tag and IL-12 is expressed with a second cell tag. 
     In some embodiments are systems for modulating the expression of a CAR and a cytokine in a host cell, comprising a first gene expression cassette comprising a first polynucleotide encoding a first polypeptide; a second gene expression cassette comprising a second polynucleotide encoding a second polypeptide; and a ligand; wherein the first polypeptide comprise one or more of: (i) a transactivation domain; (ii) a DNA-binding domain; and (iii) a ligand binding domain and the second polypeptide comprise one or more of (i) CAR; (ii) cytokine, and/or (iii) cell tag such that upon contacting the host cell with the first gene expression cassette and the second gene expression cassette in the presence of the ligand, the CAR and/or the cytokine are expressed in the host cell. In some cases, the CAR is a ROR-1 CAR and the cytokine is mbIL-15. In some cases, ROR-1 CAR and mbIL-15 are each co-expressed with a cell tag. In other cases, ROR-1 CAR is expressed with a first cell tag and mbIL-15 is expressed with a second cell tag. 
     Exemplary configurations of systems for modulating the expression of a ROR-1 CAR and a cytokine in a host cell are depicted in  FIGS. 1A-1E  and  FIGS. 2A-2E . In some embodiments, the gene expression cassettes are introduced into an immune effector cell using viral or viral based systems. Examples of non-viral based delivery systems as described herein include SB11 transposon system, the SB100X transposon system, the SB110 transposon system, the piggyBac transposon system. In one embodiment, the gene expression cassettes are introduced into an immune effector cell in one or more Sleeping Beauty transposons. 
     Exemplary embodiments of gene expression cassettes that encode for constitutive expression of ROR-1 CAR, cytokine (such as mbIL-15 or IL-12) and cell tag are depicted in  FIGS. 1A-1E .  FIGS. 1A-1B  depict exemplary gene expression cassette designs for ROR-1 CAR, mbIL-15 and cell tag in various configurations. In this embodiment, the gene expression cassette is introduced into an immune effector cell in one Sleeping Beauty transposon.  FIGS. 1C-1D  depict gene expression cassette configurations where ROR-1 CAR can be in one gene expression cassette and mbIL-15 and cell tag are in a second gene expression cassette. In this embodiment, the gene expression cassette is introduced into an immune effector cell in one or more Sleeping Beauty transposons. 
     Exemplary embodiments of gene expression cassettes that encode for expression of ROR-1 CAR, inducible cytokine (such as mbIL-15) and/or cell tag are depicted in  FIGS. 2A-2E .  FIGS. 2A-2D  depict exemplary gene expression cassette designs for ROR-1 CAR, mbIL-15 and cell tag in various configurations under the control of an inducible promoter.  FIG. 2E  is an exemplary embodiment of a gene expression cassette encoding gene-switch polypeptides as described herein. In this embodiment, the gene expression cassette(s) is introduced into an immune effector cell in one or more Sleeping Beauty transposons. 
     Ligands 
     In some embodiments, a ligand used for inducible gene switch regulation can be selected from any of, but without limitation to, following: N-[(1R)-1-(1,1-dimethylethyl)butyl]-N-(2-ethyl-3-methoxybenzoyl)-3,5-dimethylbenzohydrazide (also referred to as veledimex), (2S,3R,5R,9R,10R,13R,14S,17R)-17-[(2S,3R)-3,6-dihydroxy-6-methylheptan-2-yl]-2,3,14-trihydroxy-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one; N′-(3,5-Dimethylbenzoyl)-N′-[(3R)-2,2-dimethyl-3-hexanyl]-2-ethyl-3-methoxybenzohydrazide; 5-Methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(3,5-dimethyl-benzoyl)-N′-(1-ethyl-2,2-dimethyl-propyl)-hydrazide; 5-Methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(3,5-dimethoxy-4-methyl-benzoyl)-N′-(1-ethyl-2,2-dimethyl-propyl)-hydrazide; 5-Methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(1-tert-butyl-butyl)-N′-(3,5-dimethyl-benzoyl)-hydrazide; 5-Methyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(1-tert-butyl-butyl)-N′-(3,5-dimethoxy-4-methyl-benzoyl)-hydrazide; 5-Ethyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(3,5-dimethyl-benzoyl)-N′-(1-ethyl-2,2-dimethyl-propyl)-hydrazide; 5-Ethyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(3,5-dimethoxy-4-methyl-benzoyl)-N′-(1-ethyl-2,2-dimethyl-propyl)-hydrazide; 5-Ethyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(1-tert-butyl-butyl)-N′-(3,5-dimethyl-benzoyl)-hydrazide; 5-Ethyl-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid N′-(1-tert-butyl-butyl)-N′-(3,5-dimethoxy-4-methyl-benzoyl)-hydrazide; 3,5-Dimethyl-benzoic acid N-(1-ethyl-2,2-dimethyl-propyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide; 3,5-Dimethoxy-4-methyl-benzoic acid N-(1-ethyl-2,2-dimethyl-propyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide; 3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide; 3,5-Dimethoxy-4-methyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide; 3,5-Dimethyl-benzoic acid N-(1-ethyl-2,2-dimethyl-propyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide; 3,5-Dimethoxy-4-methyl-benzoic acid N-(1-ethyl-2,2-dimethyl-propyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide; 3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide; 3,5-Dimethoxy-4-methyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide; 2-Methoxy-nicotinic acid N-(1-tert-butyl-pentyl)-N′-(4-ethyl-benzoyl)-hydrazide; 3,5-Dimethyl-benzoic acid N-(2,2-dimethyl-1-phenyl-propyl)-N′-(4-ethyl-benzoyl)-hydrazide; 3,5-Dimethyl-benzoic acid N-(1-tert-butyl-pentyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide; and 3,5-Dimethoxy-4-methyl-benzoic acid N-(1-tert-butyl-pentyl)-N′-(3-methoxy-2-methyl-benzoyl)-hydrazide. 
     In some cases, a ligand used for dose-regulated control of ecdysone receptor-based inducible gene switch can be selected from any of, but without limitation to, an ecdysteroid, such as ecdysone, 20-hydroxyecdysone, ponasterone A, muristerone A, and the like, 9-cis-retinoic acid, synthetic analogs of retinoic acid, N,N′-diacylhydrazines such as those disclosed in U.S. Pat. Nos. 6,013,836; 5,117,057; 5,530,028; and 5,378,726 and U.S. Published Application Nos. 2005/0209283 and 2006/0020146; oxadiazolines as described in U.S. Published Application No. 2004/0171651; dibenzoylalkyl cyanohydrazines such as those disclosed in European Application No. 461,809; N-alkyl-N,N′-diaroylhydrazines such as those disclosed in U.S. Pat. No. 5,225,443; N-acyl-N-alkylcarbonylhydrazines such as those disclosed in European Application No. 234,994; N-aroyl-N-alkyl-N′-aroylhydrazines such as those described in U.S. Pat. No. 4,985,461; arnidoketones such as those described in U.S. Published Application No. 2004/0049037; each of which is incorporated herein by reference and other similar materials including 3,5-di-tert-butyl-4-hydroxy-N-isobutyl-benzamide, 8-O-acetylharpagide, oxysterols, 22(R) hydroxycholesterol, 24(S) hydroxycholesterol, 25-epoxycholesterol, T0901317, 5-alpha-6-alpha-epoxycholesterol-3-sulfate (ECHS), 7-ketocholesterol-3-sulfate, framesol, bile acids, 1,1-biphosphonate esters, juvenile hormone III, and the like. Examples of diacylhydrazine ligands useful in the present disclosure include RG-115819 (3,5-Dimethyl-benzoic acid N-(1-ethyl-2,2-dimethyl-propyl)-N′-(2-methyl-3-methoxy-benzoyl)-hydrazide-), RG-115932 ((R)-3,5-Dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide), and RG-115830 (3,5-Dimethyl-b enzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hy drazide). See, e.g., U.S. patent application Ser. No. 12/155,111, and PCT Appl. No. PCT/US2008/006757, both of which are incorporated herein by reference in their entireties. 
     Non-Viral Based Delivery Systems 
     A nucleic acid encoding a CAR described invention can also be introduced into immune effector cells using non-viral based delivery systems, such as the “Sleeping Beauty (SB) Transposon System,” which refers a synthetic DNA transposon system for introducing DNA sequences into the chromosomes of vertebrates. An exemplary SB transposon system is described for example, in U.S. Pat. Nos. 6,489,458 and 8,227,432. The Sleeping Beauty transposon system comprises a Sleeping Beauty (SB) transposase and SB transposon(s). As used herein, the Sleeping Beauty transposon system can comprise Sleeping Beauty transposase polypeptides as well as derivatives, variants and/or fragments that retain activity, and Sleeping Beauty transposon polynucleotides, derivatives, variants, and/or fragments that retain activity. In certain embodiments, the Sleeping Beauty transposase is provided as an mRNA. In some aspects, the mRNA encodes for a SB10, SB11, SB100x or SB110 transposase. In some aspects, the mRNA comprises a cap and a poly-A tail. 
     DNA transposons translocate from one DNA site to another in a simple, cut-and-paste manner. Transposition is a precise process in which a defined DNA segment is excised from one DNA molecule and moved to another site in the same or different DNA molecule or genome. As with other Tc1/mariner-type transposases, SB transposase inserts a transposon into a TA dinucleotide base pair in a recipient DNA sequence. The insertion site can be elsewhere in the same DNA molecule, or in another DNA molecule (or chromosome). In mammalian genomes, including humans, there are approximately 200 million TA sites. The TA insertion site is duplicated in the process of transposon integration. This duplication of the TA sequence is a hallmark of transposition and used to ascertain the mechanism in some experiments. The transposase can be encoded either within the transposon or the transposase can be supplied by another source, in which case the transposon becomes a non-autonomous element. Non-autonomous transposons are most useful as genetic tools because after insertion they cannot independently continue to excise and re-insert. SB transposons envisaged to be used as non-viral vectors for introduction of genes into genomes of vertebrate animals and for gene therapy. Briefly, the Sleeping Beauty (SB) system (Hackett et al., Mol Ther 18:674-83, (2010)) was adapted to genetically modify the immune effector cells (Cooper et al., Blood 105:1622-31, (2005)). In one embodiment, this involved two steps: (i) the electro-transfer of DNA plasmids expressing a SB transposon [i.e., chimeric antigen receptor (CAR) to redirect T-cell specificity (Jin et al., Gene Ther 18:849-56, (2011); Kebriaei et al., Hum Gene Ther 23:444-50, (2012)) and SB transposase and (ii) the propagation and expansion of T cells stably expressing integrants on designer artificial antigen-presenting cells (AaPC) derived from the K562 cell line (also known as AaPCs (Activating and Propagating Cells). In another, embodiment, the second step (ii) is eliminated and the genetically modified T cells are cryopreserved or immediately infused into a patient. 
     In one embodiment, the SB transposon systems are described for example in Hudecek et al., Critical Reviews in Biochemistry and Molecular Biology, 52:4, 355-380 (2017), Singh et al., Cancer Res (8):68 (2008). Apr. 15, 2008 and Maiti et al., J Immunother. 36(2): 112-123 (2013), incorporated herein by reference in their entireties. 
     In certain embodiments, a ROR-1 CAR and mbIL-15 are encoded in a transposon DNA plasmid vector, and the SB transposase is encoded in a separate vector. In certain embodiments, a ROR-1 CAR described herein is encoded in a transposon DNA plasmid vector, mb-IL15 is encoded in a second transposon DNA plasmid vector, and the SB transposase is encoded in a third DNA plasmid vector. In some embodiment, the CAR is encoded with a kill tag, for instance, HERR, HERM, CD20 or CD20t-1. In some embodiments, the mbIL-15 is encoded with a kill tag, for instance, HERR, HERM, CD20 or CD20t-1. Exemplary configurations of the ROR-1 CAR, kill tag and/or mbIL15 are depicted in  FIG. 1 . 
     In embodiments, the ROR-1 CAR can be co-expressed with mbIL-15 and the cell tag from a transposon DNA plasmid vector. In further embodiments, the ROR-1 CAR can be under the control of an inducible promoter. In another embodiment, the mbIL-15 can be under the control of an inducible promoter. In one aspect, the inducible promoter can be a gene switch ligand inducible promoter. In some cases, an inducible promoter can be a small molecule ligand-inducible two polypeptide ecdysone receptor-based gene switch, such as RHEOSWITCH® gene switch. In certain embodiments, the ROR-1 CAR, mbIL-15 and kill tag can be configured in one, two or more transposons. Exemplary configurations of the ROR-1 CAR or mbIL15 under the control of an inducible promoter are depicted in  FIG. 2 . 
     In embodiments, the ROR-1 CARs and other genetic elements are delivered to a cell using the SB11 transposon system, the SB100X transposon system, the SB110 transposon system, the piggyBac transposon system (see, e.g., U.S. Pat. No. 9,228,180, Wilson et al, “PiggyBac Transposon-mediated Gene Transfer in Human Cells,” Molecular Therapy 15:139-145 (2007), incorporated herein by reference in its entirety) and/or the piggyBat transposon system (see, e.g., Mitra et al., “Functional characterization of piggyBat from the bat  Myotis lucifugus  unveils an active mammalian DNA transposon,” Proc. Natl. Acad. Sci USA 110:234-239 (2013). Additional transposases and transposon systems are provided in U.S. Pat. Nos. 7,148,203; 8,227,432; U.S. Patent Publn. No. 2011/0117072; Mates et al., Nat Genet, 41(6):753-61 (2009). doi: 10.1038/ng.343. Epub 2009 May 3, Gene Ther., 18(9):849-56 (2011). doi: 10.1038/gt.2011.40. Epub 2011 Mar. 31 and in Ivics et al., Cell. 91(4):501-10, (1997), each of which is incorporated herein by reference in their entirety. 
     In other embodiments, the ROR-1 CAR and other genetic elements such as cytokines, mbIL-15 and/or HER1t/HER1t1/CD20/CD20t-1 tag, can be integrated into the immune effector cell&#39;s DNA through a recombinase and integrating expression vectors. Such vectors can randomly integrate into the host cell&#39;s DNA, or can include a recombination site to enable the specific recombination between the expression vector and the host cell&#39;s chromosome. Such integrating expression vectors can utilize the endogenous expression control sequences of the host cell&#39;s chromosomes to effect expression of the desired protein. In some embodiments, targeted integration is promoted by the presence of sequences on the donor polynucleotide that are homologous to sequences flanking the integration site. For example, targeted integration using the donor polynucleotides described herein can be achieved following conventional transfection techniques, e.g. techniques used to create gene knockouts or knockins by homologous recombination. In other embodiments, targeted integration is promoted both by the presence of sequences on the donor polynucleotide that are homologous to sequences flanking the integration site, and by contacting the cells with donor polynucleotide in the presence of a site-specific recombinase. By a site-specific recombinase, or simply a recombinase, it is meant a polypeptide that catalyzes conservative site-specific recombination between its compatible recombination sites. As used herein, a site-specific recombinase includes native polypeptides as well as derivatives, variants and/or fragments that retain activity, and native polynucleotides, derivatives, variants, and/or fragments that encode a recombinase that retains activity. 
     The recombinases can be introduced into a target cell before, concurrently with, or after the introduction of a targeting vector. The recombinase can be directly introduced into a cell as a protein, for example, using liposomes, coated particles, or microinjection. Alternately, a polynucleotide, either DNA or messenger RNA, encoding the recombinase can be introduced into the cell using a suitable expression vector. The targeting vector components described above are useful in the construction of expression cassettes containing sequences encoding a recombinase of interest. However, expression of the recombinase can be regulated in other ways, for example, by placing the expression of the recombinase under the control of a regulatable promoter (i.e., a promoter whose expression can be selectively induced or repressed). 
     A recombinase can be from the Integrase or Resolvase families. The Integrase family of recombinases has over one hundred members and includes, for example, FLP, Cre, and lambda integrase. The Integrase family, also referred to as the tyrosine family or the lambda integrase family, uses the catalytic tyrosine&#39;s hydroxyl group for a nucleophilic attack on the phosphodiester bond of the DNA. Typically, members of the tyrosine family initially nick the DNA, which later forms a double strand break. Examples of tyrosine family integrases include Cre, FLP, SSV1, and lambda (λ) integrase. In the resolvase family, also known as the serine recombinase family, a conserved serine residue forms a covalent link to the DNA target site (Grindley, et al., (2006) Ann Rev Biochem 16:16). 
     In one embodiment, the recombinase is an isolated polynucleotide sequence comprising a nucleic acid sequence that encodes a recombinase selecting from the group consisting of a SPβc2 recombinase, a SF370.1 recombinase, a Bxb1 recombinase, an A118 recombinase and a ϕRv1 recombinase. Examples of serine recombinases are described in detail in U.S. Pat. No. 9,034,652, hereby incorporated by reference in its entirety. 
     Recombinases for use in the practice of the present invention can be produced recombinantly or purified as previously described. Polypeptides having the desired recombinase activity can be purified to a desired degree of purity by methods known in the art of protein ammonium sulfate precipitation, purification, including, but not limited to, size fractionation, affinity chromatography, HPLC, ion exchange chromatography, heparin agarose affinity chromatography (e.g., Thorpe &amp; Smith, Proc. Nat. Acad. Sci. 95:5505-5510, 1998.) 
     In one embodiment, the recombinases can be introduced into the eukaryotic cells that contain the recombination attachment sites at which recombination is desired by any suitable method. Methods of introducing functional proteins, e.g., by microinjection or other methods, into cells are well known in the art. Introduction of purified recombinase protein ensures a transient presence of the protein and its function, which is often a preferred embodiment. Alternatively, a gene encoding the recombinase can be included in an expression vector used to transform the cell, in which the recombinase-encoding polynucleotide is operably linked to a promoter which mediates expression of the polynucleotide in the eukaryotic cell. The recombinase polypeptide can also be introduced into the eukaryotic cell by messenger RNA that encodes the recombinase polypeptide. It is generally preferred that the recombinase be present for only such time as is necessary for insertion of the nucleic acid fragments into the genome being modified. Thus, the lack of permanence associated with most expression vectors is not expected to be detrimental. One can introduce the recombinase gene into the cell before, after, or simultaneously with, the introduction of the exogenous polynucleotide of interest. In one embodiment, the recombinase gene is present within the vector that carries the polynucleotide that is to be inserted; the recombinase gene can even be included within the polynucleotide. 
     In one embodiment, a method for site-specific recombination comprises providing a first recombination site and a second recombination site; contacting the first and second recombination sites with a prokaryotic recombinase polypeptide, resulting in recombination between the recombination sites, wherein the recombinase polypeptide can mediate recombination between the first and second recombination sites, the first recombination site is attP or attB, the second recombination site is attB or attP, and the recombinase is selected from the group consisting of a  Listeria monocytogenes  phage recombinase, a  Streptococcus pyogenes  phage recombinase, a  Bacillus subtilis  phage recombinase, a  Mycobacterium tuberculosis  phage recombinase and a  Mycobacterium smegmatis  phage recombinase, provided that when the first recombination attachment site is attB, the second recombination attachment site is attP, and when the first recombination attachment site is attP, the second recombination attachment site is attB 
     Further embodiments provide for the introduction of a site-specific recombinase into a cell whose genome is to be modified. One embodiment relates to a method for obtaining site-specific recombination in an eukaryotic cell comprises providing a eukaryotic cell that comprises a first recombination attachment site and a second recombination attachment site; contacting the first and second recombination attachment sites with a prokaryotic recombinase polypeptide, resulting in recombination between the recombination attachment sites, wherein the recombinase polypeptide can mediate recombination between the first and second recombination attachment sites, the first recombination attachment site is a phage genomic recombination attachment site (attP) or a bacterial genomic recombination attachment site (attB), the second recombination attachment site is attB or attP, and the recombinase is selected from the group consisting of a  Listeria monocytogenes  phage recombinase, a  Streptococcus pyogenes  phage recombinase, a  Bacillus subtilis  phage recombinase, a  Mycobacterium tuberculosis  phage recombinase and a  Mycobacterium smegmatis  phage recombinase, provided that when the first recombination attachment site is attB, the second recombination attachment site is attP, and when the first recombination attachment site is attP, the second recombination attachment site is attB. In an embodiment the recombinase is selected from the group consisting of an A118 recombinase, a SF370.1 recombinase, a SPβc2 recombinase, a ΦRv1 recombinase, and a Bxb1 recombinase. In one embodiment the recombination results in integration. 
     Regardless of the method used to introduce exogenous nucleic acids into a host cell, in order to confirm the presence of the recombinant DNA sequence in the host cell, a variety of assays can be performed. Such assays include, for example, “molecular biological” assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; “biochemical” assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and Western blots) or by assays described herein to identify peptides or proteins or nucleic acids falling within the scope of the invention. 
     Viral Based Delivery Systems 
     Also provided herein are viral-based delivery systems, in which a nucleic acid of the present invention is inserted. Representative viral expression vectors include, but are not limited to, the adenovirus-based vectors (e.g., the adenovirus-based Per.C6 system available from Crucell, Inc. (Leiden, The Netherlands)), lentivirus-based vectors (e.g., the lentiviral-based pLPI from Life Technologies (Carlsbad, Calif.)) and retroviral vectors (e.g., the pFB-ERV plus pCFB-EGSH), herpes viruses. In an embodiment, the viral vector is a lentivirus vector. Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors have the added advantage over vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non-proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity. In general, and in embodiments, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers, (e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No. 6,326,193). 
     In embodiments, provided is a lentiviral vector comprising a backbone and a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a stalk domain; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; (e) a CD3 zeta signaling domain. Optionally, the vector further comprises a nucleic acid encoding a truncated epidermal growth factor receptor (HER1t or HERM), CD20t-1 or a full length CD20. 
     In some cases is provided a vector comprising a backbone and a nucleic acid sequence encoding (1) a truncated epidermal growth factor receptor for instance HER1t or HERt-1 or a functional variant thereof; and (2) a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and (e) a CD3 zeta signaling domain. 
     In some cases is provided a vector comprising a backbone and a nucleic acid sequence encoding (1) full length CD20, truncated CD20 or functional variants thereof, and (2) a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and (e) a CD3 zeta signaling domain. 
     In embodiments, the nucleic acid encoding the ROR-1 specific CAR is cloned into a vector comprising lentiviral backbone components. Exemplary backbone components include, but are not limited to, pFUGW, and pSMPUW. The pFUGW lentiviral vector backbone is a self inactivating (SIN) lentiviral vector backbone and has unnecessary HIV-1 viral sequences removed resulting in reduced potential for the development of neoplasia, harmful mutations, and regeneration of infectious particles. In embodiments, the vector encoding the ROR-1 CAR also encodes mbIL-15 in a single construct. In embodiments, the ROR-1 CAR and mbIL-15 are encoded on two separate lentiviral vectors. In some embodiments, the mbIL-15 is expressed with a truncated epidermal growth factor receptor tag. In embodiments, the ROR-1 CAR can be co-expressed with mbIL-15 and the cell tag from a single lentiviral vector. In further embodiments, the ROR-1 CAR can be under the control of an inducible promoter. In another embodiment, the mbIL-15 can be under the control of an inducible promoter. In one aspect, the inducible promoter can be a gene switch ligand inducible promoter. In some cases, an inducible promoter can be a small molecule ligand-inducible two polypeptide ecdysone receptor-based gene switch, such as RHEOSWITCH® gene switch. 
     In one embodiment, a ROR-1 CAR described herein comprises anti-ROR-1 scFv, human CD8 hinge and transmembrane domain, and human 4-1BB and CD3zeta signaling domains. In another embodiment, the ROR-1 CAR of the invention comprises anti-ROR-1 scFv, human CD8 hinge and transmembrane domain, human 4-1BB and CD3zeta signaling domains and optionally, a truncated epidermal growth factor receptor (HER1t or HER1t-1) tag. Other suitable vectors include integrating expression vectors, which can randomly integrate into the host cell&#39;s DNA, or can include a recombination site to enable the specific recombination between the expression vector and the host cell&#39;s chromosome. Such integrating expression vectors can utilize the endogenous expression control sequences of the host cell&#39;s chromosomes to effect expression of the desired protein. Examples of vectors that integrate in a site specific manner include, for example, components of the flp-in system from Invitrogen (Carlsbad, Calif.) (e.g., pcDNA™5/FRT), or the cre-lox system, such as can be found in the pExchange-6 Core Vectors from Stratagene (La Jolla, Calif.). Examples of vectors that randomly integrate into host cell chromosomes include, for example, pcDNA3.1 (when introduced in the absence of T-antigen) from Invitrogen (Carlsbad, Calif.), and pCI or pFN10A (ACT) FLEXI™ from Promega (Madison, Wis.). Additional promoter elements, e.g., enhancers, regulate the frequency of transcriptional initiation. Typically, these are located in the region 30-110 bp upstream of the start site, although a number of promoters have recently been shown to contain functional elements downstream of the start site as well. The spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. In the thymidine kinase (tk) promoter, the spacing between promoter elements can be increased to 50 bp apart before activity begins to decline. Depending on the promoter, it appears that individual elements can function either cooperatively or independently to activate transcription. 
     One example of a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. 
     Another example of a suitable promoter is human elongation growth factor 1 alpha 1 (hEF1a1). In embodiments, the vector construct comprising a CAR described herein comprises hEF1a1 functional variants. 
     However, other constitutive promoter sequences can also be used, including, but not limited to the simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter. Further, the invention should not be limited to the use of constitutive promoters. Inducible promoters are also contemplated as part of the invention as previously described. The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Examples of inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter. In one aspect, the inducible promoter can be a gene switch ligand inducible promoter. In some cases, an inducible promoter can be a small molecule ligand-inducible two polypeptide ecdysone receptor-based gene switch, such as RHEOSWITCH® gene switch. 
     In order to assess the expression of a CAR described herein or portions thereof, the expression vector to be introduced into a cell can also contain either a selectable marker gene or a reporter gene or both to facilitate identification and selection of expressing cells from the population of cells sought to be transfected or infected through viral vectors or non-viral vectors. In other aspects, the selectable marker can be carried on a separate piece of DNA and used in a co-transfection procedure. Both selectable markers and reporter genes can be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers include, for example, antibiotic-resistance genes, such as neomycin resistance gene (neo) and ampicillin resistance gene and the like. In some embodiments, a truncated epidermal growth factor receptor (HER1t or HER1t-1) tag can be used as a selectable marker gene. 
     Reporter genes can be used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells. Suitable reporter genes include genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tei et al., FEBS Letters 479: 79-82 (2000)). Suitable expression systems are well known and can be prepared using known techniques or obtained commercially. In general, the construct with the minimal 5′ flanking region showing the highest level of expression of reporter gene is identified as the promoter. Such promoter regions can be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription. 
     In embodiments, a viral vector described herein can comprise a hEFlal promoter to drive expression of transgenes, a bovine growth hormone polyA sequence to enhance transcription, a woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), as well as LTR sequences derived from the pFUGW plasmid. 
     Methods of introducing and expressing genes into a cell are well known. In the context of an expression vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the expression vector can be transferred into a host cell by physical, chemical, or biological means. 
     Physical methods for introducing a polynucleotide into a host cell, for instance an immune effector cell, include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and/or exogenous nucleic acids are well-known in the art. See, for example, Sambrook et al. (Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York (2001)). In embodiments, a method for the introduction of a polynucleotide into a host cell is calcium phosphate transfection or polyethylenimine (PEI) Transfection. In some embodiments, a method for introduction of a polynucleotide into a host cell is electroporation. 
     Biological methods for introducing a polynucleotide of interest into a host cell, for instance an immune effector cell, include the use of DNA and RNA vectors. Viral vectors, and especially retroviral vectors, have become the most widely used method for inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus I, adenoviruses and adeno-associated viruses, and the like. See, for example, U.S. Pat. Nos. 5,350,674 and 5,585,362. 
     Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle). 
     In the case where a viral delivery system is utilized, an exemplary delivery vehicle is a liposome. Lipid formulations can be used for the introduction of the nucleic acids into a host cell (in vitro, ex vivo, or in vivo). In another aspect, the nucleic acid can be associated with a lipid. The nucleic acid associated with a lipid can be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. Lipid, lipid/DNA or lipid/expression vector associated compositions are not limited to any particular structure in solution. For example, they can be present in a bilayer structure, as micelles, or with a “collapsed” structure. They can also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances which can be naturally occurring or synthetic lipids. For example, lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes. 
     Lipids suitable for use can be obtained from commercial sources. For example, dimyristyl phosphatidylcholine (“DMPC”) can be obtained from Sigma, St. Louis, Mo.; dicetyl phosphate (“DCP”) can be obtained from K &amp; K Laboratories (Plainview, N.Y.); cholesterol (“Chol”) can be obtained from Calbiochem-Behring; dimyristyl phosphatidylglycerol (“DMPG”) and other lipids can be obtained from Avanti Polar Lipids, Inc. (Birmingham, Ala.). Stock solutions of lipids in chloroform or chloroform/methanol can be stored at about −20′C. Chloroform is used as the only solvent since it is more readily evaporated than methanol. “Liposome” is a generic term encompassing a variety of single and multilamellar lipid vehicles formed by the generation of enclosed lipid bilayers or aggregates. Liposomes can be characterized as having vesicular structures with a phospholipid bilayer membrane and an inner aqueous medium. Multilamellar liposomes have multiple lipid layers separated by aqueous medium. They form spontaneously when phospholipids are suspended in an excess of aqueous solution. The lipid components undergo self-rearrangement before the formation of closed structures and entrap water and dissolved solutes between the lipid bilayers (Ghosh et al., Glycobiology 5: 505-10 (1991)). However, compositions that have different structures in solution than the normal vesicular structure are also encompassed. For example, the lipids can assume a micellar structure or merely exist as nonuniform aggregates of lipid molecules. Also contemplated are lipofectamine-nucleic acid complexes. 
     Cells Comprising ROR-1 CARs and Vectors 
     Provided herein are engineered cells expressing a CAR described herein. In certain embodiments, an engineered cell described herein is an immune effector cell. In embodiments, provided herein is an immune effector cell comprising a vector comprising a backbone and a nucleic acid sequence encoding ( 1 ) a truncated epidermal growth factor receptor (HER1t or HERM) and (2) a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and e) a CD3 zeta signaling domain. 
     In certain embodiments is an immune effector cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; e) a CD3 zeta signaling domain; and (f) a truncated epidermal growth factor receptor (HER1t or HERM). 
     In embodiments, provided herein is an immune effector cell comprising ( 1 ) a cell tag for use as a kill switch, selection marker, a biomarker, or a combination thereof, and (2) a chimeric antigen receptor (CAR), wherein the CAR comprises (a) a ROR-1 antigen binding domain; (b) a spacer; (c) a transmembrane domain; (d) a costimulatory signaling domain comprising 4-1BB or CD28, or both; and (e) a CD3 zeta signaling domain. In embodiments, the cell tag is HER1t, HERM, CD20t-1 or CD20. 
     In embodiments, an immune effector cell is a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell. In embodiments, the cell exhibits an anti-tumor activity when the ROR-1 antigen binding domain binds to ROR-1. 
     Modified Immune Effector Cells 
     Provided are immune effector cells modified to express one or more heterologous genes or polypeptides described herein. Provided are immune effector cells modified to express a ROR-1 CAR described herein and at least one of a HER1t, HERM, CD20 and CD20t-1 tag. In some cases is provided an immune effector cell modified to express ROR-1 CAR, mbIL-15 and at least one of a HER1t, HERM, CD20 and CD20t-1 tag disclosed herein. 
     “T cell” or “T lymphocyte” as used herein is a type of lymphocyte that plays a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells (NK cells), by the presence of a T-cell receptor (TCR) on the cell surface. 
     In some embodiments, modified immune effector cells are modified immune cells that comprise T cells and/or natural killer cells. T cells or T lymphocytes are a subtype of white blood cells that are involved in cell-mediated immunity. Exemplary T cells include T helper cells, cytotoxic T cells, TH17 cells, stem memory T cells (TSCM), naïve T cells, memory T cells, effector T cells, regulatory T cells, or natural killer T cells. 
     T helper cells (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. In some instances, TH cells are known as CD4+ T cells due to expression of the CD4 glycoprotein on the cell surfaces. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, which are expressed on the surface of antigen-presenting cells (APCs). Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. These cells can differentiate into one of several subtypes, including TH1, TH2, TH3, TH17, Th9, or TFH, which secrete different cytokines to facilitate different types of immune responses. Signaling from the APC directs T cells into particular subtypes. 
     Cytotoxic T cells (TC cells or CTLs) destroy virus-infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein on their surfaces. These cells recognize their targets by binding to antigen associated with MHC class I molecules, which are present on the surface of all nucleated cells. Through IL-10, adenosine, and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state, which prevents autoimmune diseases. 
     Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with “memory” against past infections. Memory T cells comprise subtypes: stem memory T cells (TSCM), central memory T cells (TCM cells) and two types of effector memory T cells (TEM cells and TEMRA cells). Memory cells can be either CD4+ or CD8+. Memory T cells can express the cell surface proteins CD45RO, CD45RA and/or CCR7. 
     Regulatory T cells (Treg cells), formerly known as suppressor T cells, play a role in the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress autoreactive T cells that escaped the process of negative selection in the thymus. 
     Natural killer T cells (NKT cells) bridge the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigens presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th (T helper) and Tc (cytotoxic T) cells (i.e., cytokine production and release of cytolytic/cell killing molecules). They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses. 
     Natural killer (NK) cells are a type of cytotoxic lymphocyte of the innate immune system. In some instances, NK cells provide a first line defense against viral infections and/or tumor formation. NK cells can detect MHC presented on infected or cancerous cells, triggering cytokine release, and subsequently induce lysis and apoptosis. NK cells can further detect stressed cells in the absence of antibodies and/or MHC, thereby allowing a rapid immune response. 
     Modified Immune Effector Cell Doses 
     In some embodiments, an amount of modified immune effector cells is administered to a subject in need thereof and the amount is determined based on the efficacy and the potential of inducing a cytokine-associated toxicity. In some cases, an amount of modified immune effector cells comprises about 10 2  to about 10 9  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 3  to about 10 9  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 4  to about 10 9  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 5  to about 10 9  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 5  to about 10 8  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 5  to about 10 7  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 6  to about 10 9  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 6  to about 10 8  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 7  to about 10 9  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 5  to about 10 6  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 6  to about 10 7  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 7  to about 10 8  modified immune effector cells/kg. In some cases, an amount of modified immune effector cells comprises about 10 8  to about 10 9  modified immune effector cells/kg. In some instances, an amount of modified immune effector cells comprises about 10 9  modified immune effector cells/kg. In some instances, an amount of modified immune effector cells comprises about 10 8  modified immune effector cells/kg. In some instances, an amount of modified immune effector cells comprises about 10 7  modified immune effector cells/kg. In some instances, an amount of modified immune effector cells comprises about 10 6  modified immune effector cells/kg. In some instances, an amount of modified immune effector cells comprises about 10 5  modified immune effector cells/kg. 
     In some embodiments, are CAR-T cells which are ROR-1-specific CAR-T cells. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 2  to about 10 9  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 3  to about 10 9  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 4  to about 10 9  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 5  to about 10 9  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 5  to about 10 8  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 5  to about 10 7  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 6  to about 10 9  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 6  to about 10 8  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 7  to about 10 9  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 5  to about 10 6  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 6  to about 10 7  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 7  to about 10 8  CAR-T cells/kg. In some cases, an amount of ROR-1-specific CAR-T cells comprises about 10 8  to about 10 9  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 9  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 8  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 7  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 6  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 5  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 4  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 3  CAR-T cells/kg. In some instances, an amount of ROR-1-specific CAR-T cells comprises about 10 2  CAR-T cells/kg. 
     Immune Effector Cell Sources 
     In certain aspects, the embodiments described herein include methods of making and/or expanding the antigen-specific redirected immune effector cells (e.g., T-cells, Tregs, NK-cell or NK T-cells) that comprises transfecting the cells with an expression vector containing a DNA (or RNA) construct encoding the CAR, then, optionally, stimulating the cells with feeder cells, recombinant antigen, or an antibody to the receptor to cause the cells to proliferate. In certain aspects, the cell (or cell population) engineered to express a CAR is a stem cell, iPS cell, T cell differentiated from iPS cell, immune effector cell or a precursor of these cells. 
     Sources of immune effector cells can include both allogeneic and autologous sources. In some cases immune effector cells can be differentiated from stem cells or induced pluripotent stem cells (iPSCs). Thus, cell for engineering according to the embodiments can be isolated from umbilical cord blood, peripheral blood, human embryonic stem cells, or iPSCs. For example, allogeneic T cells can be modified to include a chimeric antigen receptor (and optionally, to lack functional TCR). In some aspects, the immune effector cells are primary human T cells such as T cells derived from human peripheral blood mononuclear cells (PBMC). PBMCs can be collected from the peripheral blood or after stimulation with G-CSF (Granulocyte colony stimulating factor) from the bone marrow, or umbilical cord blood. In one aspect, the immune effector cells are Pan T cells. Following transfection or transduction (e.g., with a CAR expression construct), the cells can be immediately infused or can be cryo-preserved. In certain aspects, following transfection or transduction, the cells can be preserved in a cytokine bath that can include IL-2 and/or IL-21 until ready for infusion. In certain aspects, following transfection, the cells can be propagated for days, weeks, or months ex vivo as a bulk population within about 1, 2, 3, 4, 5 days or more following gene transfer into cells. In a further aspect, following transfection, the transfectants are cloned and a clone demonstrating presence of a single integrated or episomally maintained expression cassette or plasmid, and expression of the chimeric antigen receptor is expanded ex vivo. The clone selected for expansion demonstrates the capacity to specifically recognize and lyse antigen-expressing target cells. The recombinant T cells can be expanded by stimulation with IL-2, or other cytokines that bind the common gamma-chain (e.g., IL-7, IL-12, IL-15, IL-21, and others). The recombinant T cells can be expanded by stimulation with artificial antigen presenting cells. The recombinant T cells can be expanded on artificial antigen presenting cell or with an antibody, such as OKT3, which cross links CD3 on the T cell surface. Subsets of the recombinant T cells can be further selected with the use of magnetic bead based isolation methods and/or fluorescence activated cell sorting technology and further cultured with the AaPCs. In a further aspect, the genetically modified cells can be cryopreserved. 
     T cells can also be obtained from a number of sources, including bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, and tumors. In certain embodiments of the present invention, any number of T cell lines available in the art, can be used. In certain embodiments of the present invention, 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 Ficoll® separation. In embodiments, cells from the circulating blood of an individual are obtained by apheresis. The apheresis product typically contains lymphocytes, including T cells, monocytes, granulocytes, B cells, other nucleated white blood cells, red blood cells, and platelets. In one embodiment, the cells collected by apheresis can be washed to remove the plasma fraction and to place the cells in an appropriate buffer or media for subsequent processing steps. In one embodiment of the invention, the cells are washed with phosphate buffered saline (PBS). In an alternative embodiment, the wash solution lacks calcium and can lack magnesium or can lack many if not all divalent cations. Initial activation steps in the absence of calcium lead to magnified activation. As those of ordinary skill in the art would readily appreciate a washing step can 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 can be resuspended in a variety of biocompatible buffers, such as, for example, Ca 2+ -free, Mg 2+ -free PBS, PlasmaLyte A, or other saline solution with or without buffer. Alternatively, the undesirable components of the apheresis sample can be removed and the cells directly resuspended in culture media. 
     In another embodiment, T cells are isolated from peripheral blood lymphocytes by lysing the red blood cells and depleting the monocytes, for example, by centrifugation through a PERCOLL® gradient or by counterflow centrifugal elutriation. A specific subpopulation of T cells, such as CD3 + , CD28 + , CD4 + , CD8 + , CD45RA + , and CD45RO +  T cells, can be further isolated by positive or negative selection techniques. In another embodiment, CD14+ cells are depleted from the T-cell population. For example, in one embodiment, T cells are isolated by incubation with anti-CD3/anti-CD28 (i.e., 3×28)-conjugated beads, such as DYNABEADS® M-450 CD3/CD28 T, for a time period sufficient for positive selection of the desired T cells. In one embodiment, the time period is about 30 minutes. In a further embodiment, the time period ranges from 30 minutes to 36 hours or longer and all integer values there between. In a further embodiment, the time period is at least 1, 2, 3, 4, 5, or 6 hours. In yet another embodiment, the time period is 10 to 24 hours. In one embodiment, the incubation time period is 24 hours. For isolation of T cells from patients with leukemia, use of longer incubation times, such as 24 hours, can increase cell yield. Longer incubation times can be used to isolate T cells in any situation where there are few T cells as compared to other cell types, such in isolating tumor infiltrating lymphocytes (TIL) from tumor tissue or from immune-compromised individuals. Further, use of longer incubation times can increase the efficiency of capture of CD8+ T cells. Thus, by simply shortening or lengthening the time T cells are allowed to bind to the CD3/CD28 beads and/or by increasing or decreasing the ratio of beads to T cells (as described further herein), subpopulations of T cells can be preferentially selected for or against at culture initiation or at other time points during the process. Additionally, by increasing or decreasing the ratio of anti-CD3 and/or anti-CD28 antibodies on the beads or other surface, subpopulations of T cells can be preferentially selected for or against at culture initiation or at other desired time points. The skilled artisan would recognize that multiple rounds of selection can also be used in the context of this invention. In certain embodiments, it can be desirable to perform the selection procedure and use the “unselected” cells in the activation and expansion process. “Unselected” cells can also be subjected to further rounds of selection. 
     Enrichment of a T cell population by negative selection can be accomplished with a combination of antibodies directed to surface markers unique to the negatively selected cells. One method is cell sorting and/or selection via negative magnetic immunoadherence or flow cytometry that uses a cocktail of monoclonal antibodies directed to cell surface markers present on the cells negatively selected. For example, to enrich for CD4 +  cells by negative selection, a monoclonal antibody cocktail typically includes antibodies to CD14, CD20, CD11b, CD16, HLA-DR, and CD8. In certain embodiments, it can be desirable to enrich for or positively select for regulatory T cells which typically express CD4 + , CD25 + , CD62L hi , GITR + , and FoxP3 + . Alternatively, in certain embodiments, T regulatory cells are depleted by anti-CD25 conjugated beads or other similar method of selection. 
     For isolation of a desired population of cells by positive or negative selection, the concentration of cells and surface (e.g., particles such as beads) can be varied. In certain embodiments, it can be desirable to significantly decrease the volume in which beads and cells are mixed together (i.e., increase the concentration of cells), to ensure maximum contact of cells and beads. For example, in one embodiment, a concentration of 2 billion cells/ml is used. In one embodiment, a concentration of 1 billion cells/ml is used. In a further embodiment, greater than 100 million cells/ml is used. In a further embodiment, a concentration of cells of 10, 15, 20, 25, 30, 35, 40, 45, or 50 million cells/ml is used. In yet another embodiment, a concentration of cells from 75, 80, 85, 90, 95, or 100 million cells/ml is used. In further embodiments, concentrations of 125 or 150 million cells/ml can be used. Using high concentrations can result in increased cell yield, cell activation, and cell expansion. Further, use of high cell concentrations allows more efficient capture of cells that can weakly express target antigens of interest, such as CD28-negative T cells, or from samples where there are many tumor cells present (i.e., leukemic blood, tumor tissue, etc.). Such populations of cells can have therapeutic value and would be desirable to obtain. For example, using high concentration of cells allows more efficient selection of CD8 +  T cells that normally have weaker CD28 expression. 
     In a related embodiment, it can be desirable to use lower concentrations of cells. By significantly diluting the mixture of T cells and surface (e.g., particles such as beads), interactions between the particles and cells is minimized. This selects for cells that express high amounts of desired antigens to be bound to the particles. For example, CD4 +  T cells express higher levels of CD28 and are more efficiently captured than CD8 +  T cells in dilute concentrations. In one embodiment, the concentration of cells used is 5×10 6 /ml. In other embodiments, the concentration used can be from about 1×10 5 /ml to 1×10 6 /ml, and any integer value in between. 
     In other embodiments, the cells can be incubated on a rotator for varying lengths of time at varying speeds at either 2-10° C. or at room temperature. 
     T cells for stimulation can also be frozen after a washing step. After the washing step that removes plasma and platelets, the cells can be suspended in a freezing solution. While many freezing solutions and parameters are known in the art and will be useful in this context, one method involves using PBS containing 20% DMSO and 8% human serum albumin, or culture media containing 10% Dextran 40 and 5% Dextrose, 20% Human Serum Albumin and 7.5% DMSO, or 31.25% Plasmalyte-A, 31.25% Dextrose 5%, 0.45% NaCl, 10% Dextran 40 and 5% Dextrose, 20% Human Serum Albumin, and 7.5% DMSO or other suitable cell freezing media containing for example, Hespan and PlasmaLyte A, the cells then are frozen to −80° C. at a rate of 1° C. per minute and stored in the vapor phase of a liquid nitrogen storage tank. Other methods of controlled freezing can be used as well as uncontrolled freezing immediately at −20° C. or in liquid nitrogen. In certain embodiments, cryopreserved cells are thawed and washed as described herein and allowed to rest for one hour at room temperature prior to activation using the methods of the present invention. 
     Also provided in certain embodiments is the collection of blood samples or apheresis product from a subject at a time period prior to when the expanded cells as described herein might be needed. As such, the source of the cells to be expanded can be collected at any time point necessary, and desired cells, such as T cells, isolated and frozen for later use in T cell therapy for any number of diseases or conditions that would benefit from T cell therapy, such as those described herein. In one embodiment a blood sample or an apheresis is taken from a generally healthy subject. In certain embodiments, a blood sample or an apheresis is taken from a generally healthy subject who is at risk of developing a disease, but who has not yet developed a disease, and the cells of interest are isolated and frozen for later use. In certain embodiments, the T cells can be expanded, frozen, and used at a later time. In certain embodiments, samples are collected from a patient shortly after diagnosis of a particular disease as described herein but prior to any treatments. In a further embodiment, the cells are isolated from a blood sample or an apheresis from a subject prior to any number of relevant treatment modalities, including but not limited to treatment with agents such as natalizumab, efalizumab, antiviral agents, chemotherapy, radiation, immunosuppressive agents, such as cyclosporin, azathioprine, methotrexate, mycophenolate, and FK506, antibodies, or other immunoablative agents such as CAMPATH, anti-CD3 antibodies, cytoxan, fludarabine, cyclosporin, FK506, rapamycin, mycophenolic acid, steroids, FR901228, and irradiation. These drugs inhibit either the calcium dependent phosphatase calcineurin (cyclosporine and FK506) or inhibit the p70S6 kinase that is important for growth factor induced signaling (rapamycin) (Liu et al., Cell 66:807-815, (1991); Henderson et al., Immun 73:316-321, (1991); Bierer et al., Curr. Opin. Immun 5:763-773, (1993)). In a further embodiment, the cells are isolated for a patient and frozen for later use in conjunction with (e.g., before, simultaneously or following) bone marrow or stem cell transplantation, T cell ablative therapy using either chemotherapy agents such as, fludarabine, external-beam radiation therapy (XRT), cyclophosphamide, or antibodies such as OKT3 or CAMPATH. In another embodiment, the cells are isolated prior to and can be frozen for later use for treatment following B-cell ablative therapy such as agents that react with CD20, e.g., Rittman. 
     In a further embodiment of the present invention, T cells are obtained from a patient directly following treatment. In this regard, it has been observed that following certain cancer treatments, in particular treatments with drugs that damage the immune system, shortly after treatment during the period when patients would normally be recovering from the treatment, the quality of T cells obtained can be optimal or improved for their ability to expand ex vivo. Likewise, following ex vivo manipulation using the methods described herein, these cells can be in a preferred state for enhanced engraftment and in vivo expansion. Thus, it is contemplated within the context of the present invention to collect blood cells, including T cells, dendritic cells, or other cells of the hematopoietic lineage, during this recovery phase. Further, in certain embodiments, mobilization (for example, mobilization with GM-CSF) and conditioning regimens can be used to create a condition in a subject wherein repopulation, recirculation, regeneration, and/or expansion of particular cell types is favored, especially during a defined window of time following therapy. Illustrative cell types include T cells, B cells, dendritic cells, and other cells of the immune system. 
     Activation and Expansion of T cells 
     Whether prior to or after engineering of the T cells to express a CAR described herein, the T cells can 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. 
     Generally, the T cells described herein are expanded by contact with a surface having attached thereto an agent that stimulates a CD3/TCR complex associated signal and a ligand that stimulates a co-stimulatory molecule on the surface of the T cells. In particular, T cell populations can be stimulated as described herein, such as by contact with an anti-CD3 antibody, or antigen-binding fragment thereof, or an anti-CD2 antibody immobilized on a surface, or by contact with a protein kinase C activator (e.g., bryostatin) in conjunction with a calcium ionophore. For co-stimulation of an accessory molecule on the surface of the T cells, a ligand that binds the accessory molecule is used. For example, a population of T cells can be contacted with an anti-CD3 antibody and an anti-CD28 antibody, under conditions appropriate for stimulating proliferation of the T cells. To stimulate proliferation of either CD4 +  T cells or CD8 +  T cells, an anti-CD3 antibody and an anti-CD28 antibody. Examples of an anti-CD28 antibody include 9.3, B-T3, XR-CD28 (Diaclone, Besancon, France) can be used as can other methods commonly known in the art (Berg et al.,  Transplant Proc.  30(8):3975-3977, (1998); Haanen et al.,  J. Exp. Med.  190(9):13191328, (1999); Garland et al.,  J. Immunol Meth.  227(1-2):53-63, (1999)). 
     In certain embodiments, the primary stimulatory signal and the co-stimulatory signal for the T cell can be provided by different protocols. For example, the agents providing each signal can be in solution or coupled to a surface. When coupled to a surface, the agents can be coupled to the same surface (i.e., in “cis” formation) or to separate surfaces (i.e., in “trans” formation). Alternatively, one agent can be coupled to a surface and the other agent in solution. In one embodiment, the agent providing the co-stimulatory signal is bound to a cell surface and the agent providing the primary activation signal is in solution or coupled to a surface. In certain embodiments, both agents can be in solution. In another embodiment, the agents can be in soluble form, and then cross-linked to a surface, such as a cell expressing Fc receptors or an antibody or other binding agent which will bind to the agents. In this regard, see for example, U.S. Patent Application Publication Nos. 20040101519 and 20060034810 for artificial antigen presenting cells (aAPCs) that are contemplated for use in activating and expanding T cells in the present invention. 
     In one embodiment, the two agents are immobilized on beads, either on the same bead, i.e., “cis,” or to separate beads, i.e., “trans.” By way of example, the agent providing the primary activation signal is an anti-CD3 antibody or an antigen-binding fragment thereof and the agent providing the co-stimulatory signal is an anti-CD28 antibody or antigen-binding fragment thereof; and both agents are co-immobilized to the same bead in equivalent molecular amounts. In one embodiment, a 1:1 ratio of each antibody bound to the beads for CD4 +  T cell expansion and T cell growth is used. In certain aspects of the present invention, a ratio of anti CD3:CD28 antibodies bound to the beads is used such that an increase in T cell expansion is observed as compared to the expansion observed using a ratio of 1:1. In one particular embodiment an increase of from about 1 to about 3 fold is observed as compared to the expansion observed using a ratio of 1:1. In one embodiment, the ratio of CD3: CD28 antibody bound to the beads ranges from 100:1 to 1:100 and all integer values there between. In one aspect of the present invention, more anti-CD28 antibody is bound to the particles than anti-CD3 antibody, i.e., the ratio of CD3:CD28 is less than one. In certain embodiments of the invention, the ratio of anti CD28 antibody to anti CD3 antibody bound to the beads is greater than 2:1. In one particular embodiment, a 1:100 CD3:CD28 ratio of antibody bound to beads is used. In another embodiment, a 1:75 CD3:CD28 ratio of antibody bound to beads is used. In a further embodiment, a 1:50 CD3:CD28 ratio of antibody bound to beads is used. In another embodiment, a 1:30 CD3:CD28 ratio of antibody bound to beads is used. In embodiments, a 1:10 CD3:CD28 ratio of antibody bound to beads is used. In another embodiment, a 1:3 CD3:CD28 ratio of antibody bound to the beads is used. In yet another embodiment, a 3:1 CD3:CD28 ratio of antibody bound to the beads is used. 
     Ratios of particles to cells from 1:500 to 500:1 and any integer values in between can be used to stimulate T cells or other target cells. As those of ordinary skill in the art can readily appreciate, the ratio of particles to cells can depend on particle size relative to the target cell. For example, small sized beads could only bind a few cells, while larger beads could bind many. In certain embodiments the ratio of cells to particles ranges from 1:100 to 100:1 and any integer values in-between and in further embodiments the ratio comprises 1:9 to 9:1 and any integer values in between, can also be used to stimulate T cells. The ratio of anti-CD3- and anti-CD28-coupled particles to T cells that result in T cell stimulation can vary as noted above, however certain values include 1:100, 1:50, 1:40, 1:30, 1:20, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, and 15:1 with one ratio being at least 1:1 particles per T cell. In one embodiment, a ratio of particles to cells of 1:1 or less is used. In one particular embodiment, the particle:cell ratio is 1:5. In further embodiments, the ratio of particles to cells can be varied depending on the day of stimulation. For example, in one embodiment, the ratio of particles to cells is from 1:1 to 10:1 on the first day and additional particles are added to the cells every day or every other day thereafter for up to 10 days, at final ratios of from 1:1 to 1:10 (based on cell counts on the day of addition). In one particular embodiment, the ratio of particles to cells is 1:1 on the first day of stimulation and adjusted to 1:5 on the third and fifth days of stimulation. In another embodiment, particles are added on a daily or every other day basis to a final ratio of 1:1 on the first day, and 1:5 on the third and fifth days of stimulation. In another embodiment, the ratio of particles to cells is 2:1 on the first day of stimulation and adjusted to 1:10 on the third and fifth days of stimulation. In another embodiment, particles are added on a daily or every other day basis to a final ratio of 1:1 on the first day, and 1:10 on the third and fifth days of stimulation. One of skill in the art will appreciate that a variety of other ratios can be suitable for use in the present invention. In particular, ratios will vary depending on particle size and on cell size and type. 
     In further embodiments described herein, the immune effector cells, such as T cells, are combined with agent-coated beads, the beads and the cells are subsequently separated, and then the cells are cultured. In an alternative embodiment, prior to culture, the agent-coated beads and cells are not separated but are cultured together. In a further embodiment, the beads and cells are first concentrated by application of a force, such as a magnetic force, resulting in increased ligation of cell surface markers, thereby inducing cell stimulation. 
     By way of example, cell surface proteins can be ligated by allowing paramagnetic beads to which anti-CD3 and anti-CD28 are attached (3×28 beads) to contact the T cells. In one embodiment the cells (for example, 10 4  to 10 9  T cells) and beads (for example, DYNABEADS® M-450 CD3/CD28 T paramagnetic beads at a ratio of 1:1, or MACS® MicroBeads from Miltenyi Biotec) are combined in a buffer, for example, PBS (without divalent cations such as, calcium and magnesium). Again, those of ordinary skill in the art can readily appreciate any cell concentration can be used. For example, the target cell can be very rare in the sample and comprise only 0.01% of the sample or the entire sample (i.e., 100%) can comprise the target cell of interest. Accordingly, any cell number is within the context of the present invention. In certain embodiments, it can be desirable to significantly decrease the volume in which particles and cells are mixed together (i.e., increase the concentration of cells), to ensure maximum contact of cells and particles. For example, in one embodiment, a concentration of about 2 billion cells/ml is used. In another embodiment, greater than 100 million cells/ml is used. In a further embodiment, a concentration of cells of 10, 15, 20, 25, 30, 35, 40, 45, or 50 million cells/ml is used. In yet another embodiment, a concentration of cells from 75, 80, 85, 90, 95, or 100 million cells/ml is used. In further embodiments, concentrations of 125 or 150 million cells/ml can be used. Using high concentrations can result in increased cell yield, cell activation, and cell expansion. Further, use of high cell concentrations allows more efficient capture of cells that can weakly express target antigens of interest, such as CD28-negative T cells. Such populations of cells can have therapeutic value and would be desirable to obtain in certain embodiments. For example, using high concentration of cells allows more efficient selection of CD8+ T cells that normally have weaker CD28 expression. 
     In one embodiment described herein, the mixture can be cultured for several hours (about 3 hours) to about 14 days or any hourly integer value in between. In another embodiment, the mixture can be cultured for 21 days. In one embodiment of the invention the beads and the T cells are cultured together for about eight days. In another embodiment, the beads and T cells are cultured together for 2-3 days. Several cycles of stimulation can also be desired such that culture time of T cells can be 60 days or more. Conditions appropriate for T cell culture include an appropriate media (e.g., Minimal Essential Media or RPMI Media 1640 or, X-vivo 15, (Lonza)) that can contain factors necessary for proliferation and viability, including serum (e.g., fetal bovine or human serum), interleukin-2 (IL-2), insulin, IFN-.gamma., IL-4, IL-7, GM-CSF, IL-10, IL-12, IL-15, TGFbeta, and TNF-alpha or any other additives for the growth of cells known to the skilled artisan. Other additives for the growth of cells include, but are not limited to, surfactant, plasmanate, and reducing agents such as N-acetyl-cysteine and 2-mercaptoethanol. Media can include RPMI 1640, AIM-V, DMEM, MEM, alpha-MEM, F-12, X-Vivo 15, and X-Vivo 20, Optimizer, with added amino acids, sodium pyruvate, and vitamins, either serum-free or supplemented with an appropriate amount of serum (or plasma) or a defined set of hormones, and/or an amount of cytokine(s) sufficient for the growth and expansion of T cells. Antibiotics, e.g., penicillin and streptomycin, are included only in experimental cultures, not in cultures of cells that are to be infused into a subject. The target cells are maintained under conditions necessary to support growth, for example, an appropriate temperature (e.g., 37° C.) and atmosphere (e.g., air plus 5% CO2). 
     T cells that have been exposed to varied stimulation times can exhibit different characteristics. For example, typical blood or apheresed peripheral blood mononuclear cell products have a helper T cell population (T H , CD4 + ) that is greater than the cytotoxic or suppressor T cell population (Tc, CD8 + ). Ex vivo expansion of T cells by stimulating CD3 and CD28 receptors produces a population of T cells that prior to about days 8-9 consists predominately of T H  cells, while after about days 8-9, the population of T cells comprises an increasingly greater population of Tc cells. Accordingly, depending on the purpose of treatment, infusing a subject with a T cell population comprising predominately of T H  cells can be advantageous. Similarly, if an antigen-specific subset of T C  cells has been isolated it can be beneficial to expand this subset to a greater degree. 
     Further, in addition to CD4 and CD8 markers, other phenotypic markers vary significantly, but in large part, reproducibly during the course of the cell expansion process. Thus, such reproducibility enables the ability to tailor an activated T cell product for specific purposes. 
     In some cases, immune effector cells of the embodiments (e.g., T-cells) are co-cultured with activating and propagating cells (AaPCs), to aid in cell expansion. AaPCs can also be referred to as artificial Antigen Presenting cells (aAPCs). For example, antigen presenting cells (APCs) are useful in preparing therapeutic compositions and cell therapy products of the embodiments. In one aspect, the AaPCs can be genetically modified K562 cells. For general guidance regarding the preparation and use of antigen-presenting systems, see, e.g., U.S. Pat. Nos. 6,225,042, 6,355,479, 6,362,001 and 6,790,662; U.S. Patent Application Publication Nos. 2009/0017000 and 2009/0004142; and International Publication No. WO2007/103009, each of which is incorporated by reference. In yet a further aspect of the embodiments, culturing the genetically modified CAR cells comprises culturing the genetically modified CAR cells in the presence of dendritic cells or activating and propagating cells (AaPCs) that stimulate expansion of the CAR-expressing immune effector cells. In still further aspects, the AaPCs comprise a CAR-binding antibody or fragment thereof expressed on the surface of the AaPCs. The AaPCs can comprise additional molecules that activate or co-stimulate T-cells in some cases. The additional molecules can, in some cases, comprise membrane-bound Cy cytokines. In yet still further aspects, the AaPCs are inactivated or irradiated, or have been tested for and confirmed to be free of infectious material. In still further aspects, culturing the genetically modified CAR cells in the presence of AaPCs comprises culturing the genetically modified CAR cells in a medium comprising soluble cytokines, such as IL-15, IL-21 and/or IL-2. The cells can be cultured at a ratio of about 10:1 to about 1:10; about 3:1 to about 1:5; about 1:1 to about 1:3 (immune effector cells to AaPCs); or any range derivable therein. For example, the co-culture of T cells and AaPCs can be at a ratio of about 1:1, about 1:2 or about 1:3. 
     In one aspect, the AaPCs can express CD137L. In some aspects, the AaPCs can further express the antigen that is targeted by the CAR cell, for example ROR-1 (full length, truncate or any variant thereof. In other aspects, the AaPCs can further express CD64, CD86, or mIL15. In certain aspects, the AaPCs can express at least one anti-CD3 antibody clone, such as, for example, OKT3 and/or UCHT1. In one aspect, the AaPCs can be inactivated (e.g., irradiated). In one aspect, the AaPCs can have been tested for and confirmed to be free of infectious material. Methods for producing such AaPCs are known in the art. In one aspect, culturing the CAR-modified T cell population with AaPCs can comprise culturing the cells at a ratio of about 10:1 to about 1:10; about 3:1 to about 1:5; about 1:1 to about 1:3 (T cells to AaPCs); or any range derivable therein. For example, the co-culture of T cells and AaPCs can be at a ratio of about 1:1, about 1:2 or about 1:3. In one aspect, the culturing step can further comprise culturing with an aminobisphosphonate (e.g., zoledronic acid). 
     In one aspect, the population of genetically modified CAR cells is immediately infused into a subject or cryopreserved. In another aspect, the population of genetically modified CAR cells is placed in a cytokine bath prior to infusion into a subject. In a further aspect, the population of genetically modified CAR cells is cultured and/or stimulated for no more than 1, 2, 3, 4, 5, 6, 7, 14, 21, 28, 35 42 days, 49, 56, 63 or 70 days. In an embodiment, a stimulation includes the co-culture of the genetically modified CAR T cells with AaPCs to promote the growth of CAR positive T cells. In another aspect, the population of genetically modified CAR cells is stimulated for not more than: 1X stimulation, 2X stimulation, 3X stimulation, 4X stimulation, 5X stimulation, 5X stimulation, 6X stimulation, 7X stimulation, 8X stimulation, 9X stimulation or 10X stimulation. In some instances, the genetically modified cells are not cultured ex vivo in the presence of AaPCs. In some specific instances, the method of the embodiment further comprises enriching the cell population for CAR-expressing immune effector cells (e.g., T-cells) after the transfection and/or culturing step. The enriching can comprise fluorescence-activated cell sorting (FACS) to sort for CAR-expressing cells. In a further aspect, the sorting for CAR-expressing cells comprises use of a CAR-binding antibody. The enriching can also comprise depletion of CD56+ cells. In yet still a further aspect of the embodiment, the method further comprises cryopreserving a sample of the population of genetically modified CAR cells. 
     In some cases, AaPCs are incubated with a peptide of an optimal length that allows for direct binding of the peptide to the MHC molecule without additional processing. Alternatively, the cells can express an antigen of interest (i.e., in the case of MHC-independent antigen recognition). Furthermore, in some cases, APCs can express an antibody that binds to either a specific CAR polypeptide or to CAR polypeptides in general (e.g., a universal activating and propagating cell (uAPC). Such methods are disclosed in WO/2014/190273, which is incorporated herein by reference. In addition to peptide-MHC molecules or antigens of interest, the AaPC systems can also comprise at least one exogenous assisting molecule. Any suitable number and combination of assisting molecules can be employed. The assisting molecule can be selected from assisting molecules such as co-stimulatory molecules and adhesion molecules. Exemplary co-stimulatory molecules include CD70 and B7.1 (B7.1 was previously known as B7 and also known as CD80), which among other things, bind to CD28 and/or CTLA-4 molecules on the surface of T cells, thereby affecting, for example, T-cell expansion, Th1 differentiation, short-term T-cell survival, and cytokine secretion such as interleukin (IL)-2. Adhesion molecules can include carbohydrate-binding glycoproteins such as selectins, transmembrane binding glycoproteins such as integrins, calcium-dependent proteins such as cadherins, and single-pass transmembrane immunoglobulin (Ig) superfamily proteins, such as intercellular adhesion molecules (ICAMs) that promote, for example, cell-to-cell or cell-to-matrix contact. Exemplary adhesion molecules include LFA-3 and ICAMs, such as ICAM-1. Techniques, methods, and reagents useful for selection, cloning, preparation, and expression of exemplary assisting molecules, including co-stimulatory molecules and adhesion molecules, are exemplified in, e.g., U.S. Pat. Nos. 6,225,042, 6,355,479, and 6,362,001, incorporated herein by reference. 
     Cells selected to become AaPCs, preferably have deficiencies in intracellular antigen-processing, intracellular peptide trafficking, and/or intracellular MHC Class I or Class II molecule-peptide loading, or are poikilothermic (i.e., less sensitive to temperature challenge than mammalian cell lines), or possess both deficiencies and poikilothermic properties. Preferably, cells selected to become AaPCs also lack the ability to express at least one endogenous counterpart (e.g., endogenous MHC Class I or Class II molecule and/or endogenous assisting molecules as described above) to the exogenous MHC Class I or Class II molecule and assisting molecule components that are introduced into the cells. Furthermore, AaPCs preferably retain the deficiencies and poikilothermic properties that were possessed by the cells prior to their modification to generate the AaPCs. Exemplary AaPCs either constitute or are derived from a transporter associated with antigen processing (TAP)-deficient cell line, such as an insect cell line. An exemplary poikilothermic insect cells line is a  Drosophila  cell line, such as a Schneider 2 cell line (see, e.g., Schneider 1972 Illustrative methods for the preparation, growth, and culture of Schneider 2 cells, are provided in U.S. Pat. Nos. 6,225,042, 6,355,479, and 6,362,001. 
     In one embodiment, AaPCs are also subjected to a freeze-thaw cycle. In an exemplary freeze-thaw cycle, the AaPCs can be frozen by contacting a suitable receptacle containing the AaPCs with an appropriate amount of liquid nitrogen, solid carbon dioxide (i.e., dry ice), or similar low-temperature material, such that freezing occurs rapidly. The frozen APCs are then thawed, either by removal of the AaPCs from the low-temperature material and exposure to ambient room temperature conditions, or by a facilitated thawing process in which a lukewarm water bath or warm hand is employed to facilitate a shorter thawing time. Additionally, AaPCs can be frozen and stored for an extended period of time prior to thawing. Frozen AaPCs can also be thawed and then lyophilized before further use. Preferably, preservatives that might detrimentally impact the freeze-thaw procedures, such as dimethyl sulfoxide (DMSO), polyethylene glycols (PEGs), and other preservatives, are absent from media containing AaPCs that undergo the freeze-thaw cycle, or are essentially removed, such as by transfer of AaPCs to media that is essentially devoid of such preservatives. 
     In further embodiments, xenogenic nucleic acid and nucleic acid endogenous to the AaPCs, can be inactivated by crosslinking, so that essentially no cell growth, replication or expression of nucleic acid occurs after the inactivation. In one embodiment, AaPCs are inactivated at a point subsequent to the expression of exogenous MHC and assisting molecules, presentation of such molecules on the surface of the AaPCs, and loading of presented MHC molecules with selected peptide or peptides. Accordingly, such inactivated and selected peptide loaded AaPCs, while rendered essentially incapable of proliferating or replicating, retain selected peptide presentation function. Preferably, the crosslinking also yields AaPCs that are essentially free of contaminating microorganisms, such as bacteria and viruses, without substantially decreasing the antigen-presenting cell function of the AaPCs. Thus crosslinking maintains the important AaPC functions of while helping to alleviate concerns about safety of a cell therapy product developed using the AaPCs. For methods related to crosslinking and AaPCs, see for example, U.S. Patent Application Publication No. 20090017000, which is incorporated herein by reference. 
     In certain embodiments there are further provided an engineered antigen presenting cell (APC). Such cells can be used, for example, as described above, to propagate immune effector cells ex vivo. In further aspects, engineered APCs can, themselves be administered to a patient and thereby stimulate expansion of immune effector cells in vivo. Engineered APCs of the embodiments can, themselves, be used as a therapeutic agent. In other embodiments, the engineered APCs can used as a therapeutic agent that can stimulate activation of endogenous immune effector cells specific for a target antigen and/or to increase the activity or persistence of adoptively transferred immune effector cells specific to a target antigen. 
     As used herein the term “engineered APC” refers to cell(s) that comprises at least a first transgene, wherein the first transgene encodes a HLA. Such engineered APCs can further comprise a second transgene for expression of an antigen, such that the antigen is presented at the surface on the APC in complex with the HLA. In some aspects, the engineered APC can be a cell type that presented antigens (e.g., a dendritic cell). In further aspects, engineered APC can be produced from a cell type that does not normally present antigens, such a T-cell or T-cell progenitor (referred to as “T-APC”). Thus, in some aspects, an engineered APC of the embodiments comprises a first transgene encoding a target antigen and a second transgene encoding a human leukocyte antigen (HLA), such that the HLA is expressed on the surface of the engineered APC in complex with an epitope of the target antigen. In certain specific aspects, the HLA expressed in the engineered APC is HLA-A2. 
     In some aspects, an engineered APC of the embodiments can further comprise at least a third transgene encoding co-stimulatory molecule. The co-stimulatory molecule can be a co-stimulatory cytokine that can be a membrane-bound Cy cytokine. In certain aspects, the co-stimulatory cytokine is IL-15, such as membrane-bound IL-15. In some further aspects, an engineered APC can comprise an edited (or deleted) gene. For example, an inhibitory gene, such as PD-1, LIM-3, CTLA-4 or a TCR, can be edited to reduce or eliminate expression of the gene. An engineered APC of the embodiments can further comprise a transgene encoding any target antigen of interest. 
     Point-Of-Care 
     In one embodiment of the present disclosure, the immune effector cells described herein are modified at a point-of-care site. In some cases, modified immune effector cells are also referred to as engineered T cells. In some cases, the point-of-care site is at a hospital or at a facility (e.g., a medical facility) near a subject in need of treatment. The subject undergoes apheresis and peripheral blood mononuclear cells (PBMCs) or a sub population of PBMC can be enriched for example, by elutriation or Ficoll separation. Enriched PBMC or a subpopulation of PBMC can be cryopreserved in any appropriate cryopreservation solution prior to further processing. In one instance, the elutriation process is performed using a buffer solution containing human serum albumin. Immune effector cells, such as T cells can be isolated by selection methods described herein. In one instance, the selection method for T cells includes beads specific for CD3 or beads specific for CD4 and CD8 on T cells. In one case, the beads can be paramagnetic beads. The harvested immune effector cells can be cryopreserved in any appropriate cryopreservation solution prior to modification. The immune effector cells can be thawed up to 24 hours, 36 hours, 48 hours. 72 hours or 96 hours ahead of infusion. The thawed cells can be placed in cell culture buffer, for example in cell culture buffer (e.g. RPMI) supplemented with fetal bovine serum (FBS) or human serum AB or placed in a buffer that includes cytokines such as IL-2 and IL-21, prior to modification. In another aspect, the harvested immune effector cells can be modified immediately without the need for cryopreservation. 
     In some cases, the immune effector cells are modified by engineering/introducing a chimeric receptor, one or more cell tag(s), and/or cytokine(s) into the immune effector cells and then rapidly infused into a subject. In some cases, the sources of immune effector cells can include both allogeneic and autologous sources. In one case, the immune effector cells can be T cells or NK cells. In one case, the chimeric receptor can be a ROR-1 CAR. In another case, the cytokine can be mbIL-15. In one case, the mbIL-15 is of SEQ ID NO: 113, or variant or fragment thereof. In yet another case, expression of mbIL-15 is modulated by ligand inducible gene-switch expression systems described herein. For example, a ligand such as veledimex can be delivered to the subject to modulate the expression of mbIL-15. In another case, the cytokine can be IL-12. In yet another case, expression of IL-12 is modulated by ligand inducible gene-switch expression systems described herein. For example, a ligand such as veledimex can be delivered to the subject to modulate the expression of IL-12. 
     In another aspect, veledimex is provided at 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg or 100 mg. In a further aspect, lower doses of veledimex are provided, for example, 0.5 mg, 1 mg, 5 mg, 10 mg, 15 mg or 20 mg. In one embodiment, veledimex is administered to the subject 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 days prior to infusion of the modified immune effector cells. In a further embodiment, veledimex is administered about once every 12 hours, about once every 24 hours, about once every 36 hours or about once every 48 hours, for an effective period of time to a subject post infusion of the modified immune effector cells. In one embodiment, an effective period of time for veledimex administration is about: 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 days. In other embodiments, veledimex can be re-administered after a rest period, after a drug holiday or when the subject experiences a relapse. 
     In certain cases, where an adverse effect on a subject is observed or when treatment is not needed, the cell tag can be activated, for example via cetuximab, for conditional in vivo ablation of modified immune effector cells comprising cell tags such as truncated epidermal growth factor receptor tags as described herein. 
     In some embodiments, such immune effectors cells are modified by the constructs as described in  FIGS. 1-2  through electroporation. In one instance, electroporation is performed with electroporators such as Lonza&#39;s Nucleofector™ electroporators. In other embodiments, the vector comprising the above-mentioned constructs is a non-viral or viral vector. In one case, the non-viral vector includes a Sleeping Beauty transposon-transposase system. In one instance, the immune effector cells are electroporated using a specific sequence. For example, the immune effector cells can be electroporated with one transposon followed by the DNA encoding the transposase followed by a second transposon. In another instance, the immune effector cells can be electroporated with all transposons and transposase at the same time. In another instance, the immune effector cells can be electroporated with a transposase followed by both transposons or one transposon at a time. While undergoing sequential electroporation, the immune effector cells can be rested for a period of time prior to the next electroporation step. 
     In some cases, the modified immune effector cells do not undergo a propagation and activation step. In some cases, the modified immune effector cells do not undergo an incubation or culturing step (e.g. ex vivo propagation). In certain cases, the modified immune effector cells are placed in a buffer that includes IL-2 and IL21 prior to infusion. In other instances, the modified immune effector cells are placed or rested in cell culture buffer, for example in cell culture buffer (e.g. RPMI) supplemented with fetal bovine serum (FBS) prior to infusion. Prior to infusion, the modified immune effector cells can be harvested, washed and formulated in saline buffer in preparation for infusion into the subject. 
     In one instance, the subject has been lymphodepleted prior to infusion. In other instances, lymphodepletion is not required and the modified immune effector cells are rapidly infused into the subject. Exemplary lymphodepletion regimens are listed in Tables 2 and 3 below: 
     
       
         
           
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 Regimen 1 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                 D-6 
                 Admit/IV Hydration 
               
               
                 D-5 
                 Fludarabine 25 mg/m2, Cyclophosphamide 250 mg/m2 
               
               
                 D-4 
                 Fludarabine 25 mg/m2, Cyclophosphamide 250 mg/m2 
               
               
                 D-3 
                 Fludarabine 25 mg/m2 IV, Cyclophosphamide 250 mg/m2 
               
               
                 D-2 
                 REST 
               
               
                 D-1 
                 REST 
               
               
                 D0 
                 T-cell infusion 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 Regimen 2 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                 D-6 
                 Admit/IV Hydration 
               
               
                 D-5 
                 Fludarabine 30 mg/m2, Cyclophosphamide 500 mg/m2 
               
               
                 D-4 
                 Fludarabine 30 mg/m2, Cyclophosphamide 500 mg/m2 
               
               
                 D-3 
                 Fludarabine 30 mg/m2 IV, Cyclophosphamide 500 mg/m2 
               
               
                 D-2 
                 REST 
               
               
                 D-1 
                 REST 
               
               
                 D0 
                 T-cell infusion 
               
               
                   
               
            
           
         
       
     
     In a further instance, the subject undergoes minimal lymphodepletion. Minimal lymphodepletion herein refers to a reduced lymphodepletion protocol such that the subject can be infused within 1 day, 2 days or 3 days following the lymphodepletion regimen. In one instance, a reduced lymphodepletion protocol can include lower doses of fludarabine and/or cyclophosphamide. In another instance, a reduced lymphodepletion protocol can include a shortened period of lymphodepletion, for example 1 day or 2 days. 
     In one embodiment, the immune effector cells are modified by engineering/introducing a chimeric receptor and a cytokine into said immune effector cells and then rapidly infused into a subject. In other cases, the immune effector cells are modified by engineering/introducing a chimeric receptor and a cytokine into said cells and then infused within at least: 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 hours into a subject. In other cases, immune effector cells are modified by engineering/introducing a chimeric receptor and a cytokine into the immune effector cells and then infused in 0 days, &lt;1 day, &lt;2 days, &lt;3 days, &lt;4 days, &lt;5 days, &lt;6 days or &lt;7 days into a subject. 
     In some embodiments, an amount of modified effector cells is administered to a subject in need thereof and the amount is determined based on the efficacy and the potential of inducing a cytokine-associated toxicity. In another embodiment, the modified effector cells are CAR +  and CD3 +  cells. In some cases, an amount of modified effector cells comprises about 10 4  to about 10 9  modified effector cells/kg. In some cases, an amount of modified effector cells comprises about 10 4  to about 10 5  modified effector cells/kg. In some cases, an amount of modified effector cells comprises about 10 5  to about 10 6  modified effector cells/kg. In some cases, an amount of modified effector cells comprises about 10 6  to about 10′ modified effector cells/kg. In some cases, an amount of modified effector cells comprises &gt;10 4  but ≤10 5  modified effector cells/kg. In some cases, an amount of modified effector cells comprises &gt;10 5  but ≤10 6  modified effector cells/kg. In some cases, an amount of modified effector cells comprises &gt;10 6  but ≤10′ modified effector cells/kg. 
     In one embodiment, the modified immune effector cells are targeted to the cancer via regional delivery directly to the tumor tissue. For example, in ovarian cancer, the modified immune effector cells can be delivered intraperitoneally (IP) to the abdomen or peritoneal cavity. Such IP delivery can be performed via a port or pre-existing port placed for delivery of chemotherapy drugs. Other methods of regional delivery of modified immune effector cells can include catheter infusion into resection cavity, ultrasound guided intratumoral injection, hepatic artery infusion or intrapleural delivery. 
     In one embodiment, a subject in need thereof, can begin therapy with a first dose of modified immune effector cells delivered via IP followed by a second dose of modified immune effector cells delivered via IV. In a further embodiment, the second dose of modified immune effector cells can be followed by subsequent doses which can be delivered via IV or IP. In one embodiment, the duration between the first and second or further subsequent dose can be about: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 days. In one embodiment, the duration between the first and second or further subsequent dose can be about: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 months. In another embodiment, the duration between the first and second or further subsequent dose can be about: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 years. 
     In another embodiment, a catheter can be placed at the tumor or metastasis site for further administration of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 doses of modified immune effector cells. In some cases, doses of modified effector cells can comprise about 10 2  to about 10 9  modified effector cells/kg. In cases where toxicity is observed, doses of modified effector cells can comprise about 10 2  to about 10 5  modified effector cells/kg. In some cases, doses of modified effector cells can start at about 10 2  modified effector cells/kg and subsequent doses can be increased to about: 10 4 , 10 5 , 10 6 , 10′, 10 8  or 10 9  modified effector cells/kg. 
     In other embodiments, a method of stimulating the proliferation and/or survival of engineered cells comprises obtaining a sample of cells from a subject, and transfecting cells of the sample of cells with one or more polynucleotides that comprise one or more transposons. In one embodiment, the transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, and a transposase effective to integrate said one or more polynucleotides into the genome of said cells, to provide a population of engineered cells. In an embodiment, the transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, gene switch polypeptides for ligand-inducible control of the cytokine and a transposase effective to integrate said one or more polynucleotides into the genome of said cells, to provide a population of engineered cells. In an embodiment, the gene switch polypeptides comprise i) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain, and ii) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain. In some embodiments, the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. In one instance, lymphodepletion is not required prior to administration of the engineered cells to a subject. 
     In one instance, a method of in vivo propagation of engineered cells comprises obtaining a sample of cells from a subject, and transfecting cells of the sample of cells with one or more polynucleotides that comprise one or more transposons. In one embodiment, the transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, and a transposase effective to integrate said one or more polynucleotides into the genome of said cells, to provide a population of engineered cells. In an embodiment, the transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, gene switch polypeptides for ligand-inducible control of the cytokine and a transposase effective to integrate said one or more polynucleotides into the genome of said cells, to provide a population of engineered cells. In an embodiment, the gene switch polypeptides comprise i) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain, and ii) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain. In some embodiments, the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. In one instance, lymphodepletion is not required prior to administration of the engineered cells to a subject. 
     In another embodiment, a method of enhancing in vivo persistence of engineered cells in a subject in need thereof comprises obtaining a sample of cells from a subject, and transfecting cells of the sample of cells with one or more polynucleotides that comprise one or more transposons. In some cases, one or more transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, and a transposase effective to integrate the DNA into the genome of said cells, to provide a population of engineered cells. In some cases, one or more transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, gene switch polypeptides for ligand-inducible control of the cytokine and a transposase effective to integrate the DNA into the genome of said cells, to provide a population of engineered cells. In some cases, the gene switch polypeptides comprise i) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain, and ii) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain, wherein the first gene switch polypeptide and the second gene switch polypeptide are connected by a linker. In one instance, lymphodepletion is not required prior to administration of the engineered cells to a subject. 
     In another embodiment, a method of treating a subject with a solid tumor comprises obtaining a sample of cells from a subject, transfecting cells of the sample with one or more polynucleotides that comprise one or more transposons, and administering the population of engineered cells to the subject. In one instance, lymphodepletion is not required prior to administration of the engineered cells to a subject. In some cases, the one or more transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, and a transposase effective to integrate the DNA into the genome of the cells. In some cases, the one or more transposons encode a chimeric antigen receptor (CAR), a cytokine, one or more cell tags, gene switch polypeptides for ligand-inducible control of the cytokine and a transposase effective to integrate the DNA into the genome of the cells. In some cases, the gene switch polypeptides comprise: i) a first gene switch polypeptide that comprises a DNA binding domain fused to a first nuclear receptor ligand binding domain, and ii) a second gene switch polypeptide that comprises a transactivation domain fused to a second nuclear receptor ligand binding domain, wherein the first gene switch polypeptide and second gene switch polypeptide are connected by a linker. In some cases, the cells are transfected via electroporation. In some cases, the polynucleotides encoding the gene switch polypeptides are modulated by a promoter. In some cases, the promoter is a tissue-specific promoter or an EF1A promoter or functional variant thereof. In some cases, the tissue-specific promoter comprises a T cell specific response element or an NFAT response element. In some cases, the cytokine comprises at least one of IL-1, IL-2, IL-15, IL-12, IL-21, a fusion of IL-15, IL-15R or an IL-15 variant. In some cases, the cytokine is in secreted form. In some cases, the cytokine is in membrane-bound form. In some cases, the cells are NK cells, NKT cells, T-cells or T-cell progenitor cells. In some cases, the cells are administered to a subject (e.g. by infusing the subject with the engineered cells). In some cases, the method further comprises administering an effective amount of a ligand (e.g. veledimex) to induce expression of the cytokine. In some cases, the CAR is capable of binding at least ROR1. In some cases, the transposase is salmonid-type Tc1-like transposase. In some cases, the transposase is SB11 or SB100x transposase. In other cases, the transposase is PiggyBac. In some cases, the cell tag comprises at least one of a HER1 truncated variant or a CD20 truncated variant. 
     Therapeutic Applications 
     In embodiments described herein, is an immune effector cell (e.g., T cell) transduced with Sleeping Beauty transposon(s) and Sleeping Beauty transposase. For example, the Sleeping Beauty transposon or transposons can include a CAR that combines an antigen recognition domain of ROR-1 with a spacer of CD8 alpha hinge and variants thereof, an intracellular domain of CD3-zeta, CD28, 4-1BB, or any combinations thereof and the intracellular domain CD3zeta, one or more cell tags, one or more cytokines and optionally, components of the gene switch system as described herein. Therefore, in some instances, the transduced T cell can elicit a CAR-mediated T-cell response. 
     In embodiments described herein, is provided the use of a CAR to redirect the specificity of a primary T cell to a ROR-1 surface antigen. Thus, the present invention also provides a method for stimulating a T cell-mediated immune response to a target cell population or tissue in a mammal comprising the step of administering to the mammal a T cell that expresses a CAR, wherein the CAR comprises a binding moiety that specifically interacts with ROR-1, a spacer, a zeta chain portion comprising for example the intracellular domain of human CD3zeta, and a costimulatory signaling region. 
     In one embodiment, the present disclosure includes a cellular therapy where T cells are genetically modified to express the ROR-1-specific CARs of the invention and the CART cell is infused to a recipient in need thereof. The infused cell is able to kill cells overexpressing ROR-1 in the recipient. Unlike antibody therapies, CAR T cells as described herein are able to replicate in vivo resulting in long-term persistence that can lead to sustained effect on tumor cells. 
     The invention additionally provides a method for detecting a disease that comprises overexpression of ROR-1 in a subject, comprising a) providing i) a sample from a subject, and ii) any one or more of the antibodies, or antigen-binding fragments thereof, that are described herein, b) contacting the sample with the antibody under conditions for specific binding of the antibody with its antigen, and c) detecting an increased level of binding of the antibody to the sample compared to a control sample lacking the disease, thereby detecting the disease in the subject. In one embodiment, the disease is cancer. In a preferred embodiment, the cancer is selected from the group of ovarian cancer and breast cancer. While not intending to limit the method of detection, in one embodiment, detecting binding of the antibody to the sample is immunohistochemical, enzyme-linked immunosorbent assay (ELISA), fluorescence-activated cell sorting (FACS), Western blot, immunoprecipitation, and/or radiographic imaging. 
     Also provided herein is a method for treating a disease that comprises overexpression of ROR-1, comprising administering to a subject having the disease a therapeutically effective amount of any one or more of the antibodies, or antigen-binding fragments thereof, that are described herein. In one embodiment, the disease is cancer, as exemplified by ovarian cancer and breast cancer. 
     In one embodiment, the ROR-1 CAR T cells described herein can undergo robust in vivo T cell expansion and can persist for an extended amount of time. In another embodiment, the CAR T cells described herein can evolve into specific memory T cells that can be reactivated. 
     The CAR-modified T cells described herein can also serve as a type of vaccine for ex vivo immunization and/or in vivo therapy in a mammal. In embodiments, the mammal is a human. With respect to ex vivo immunization, at least one of the following occurs in vitro prior to administering the immune effector cell into a mammal: i) expansion of the cells, ii) introducing a nucleic acid encoding a CAR to the cells, and/or iii) cryopreservation of the cells. 
     Ex vivo procedures are well known and are discussed more fully below. Briefly, cells are isolated from a mammal (for example, a human) and genetically modified (i.e., transduced or transfected in vitro) with a vector expressing a CAR disclosed herein. The CAR-modified cell can be administered to a mammalian recipient to provide a therapeutic benefit. The mammalian recipient can be a human and the CAR-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 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. 
     In addition to using a cell-based vaccine in terms of ex vivo immunization, the present invention also provides compositions and methods for in vivo immunization to elicit an immune response directed against an antigen in a patient. 
     Generally, the cells activated and expanded as described herein can be utilized in the treatment and prevention of diseases that arise in individuals who are immunocompromised. In particular, the CAR-modified T cells of the invention are used in the treatment of ROR-1 malignancies, such as for example, ROR-1. In certain embodiments, the cells of the invention are used in the treatment of patients at risk for developing ROR-1. Thus, the methods for the treatment or prevention of ROR-1 comprising administering to a subject in need thereof, a therapeutically effective amount of the CAR-modified T cells of the invention. In embodiments, the cells activated and expanded as described herein can be utilized in the treatment of ROR-1. 
     Briefly, pharmaceutical compositions described herein can comprise a target cell population as described herein, in combination with one or more pharmaceutically or physiologically acceptable carriers, diluents or excipients. Such compositions can 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. In embodiments, compositions of the present invention are formulated for intravenous administration. 
     Pharmaceutical compositions described herein can 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, although appropriate dosages can be determined by clinical trials. 
     When “an immunologically effective amount”, or “therapeutic amount” is indicated, the precise amount of the compositions described herein to be administered can be determined by a physician with consideration of individual differences in age, weight, and condition of the patient (subject). It can generally be stated that a pharmaceutical composition comprising the T cells described herein can be administered at a dosage of 10 4  to 10 9  cells/kg body weight, 10 5  to 10 6  cells/kg body weight, including all integer values within those ranges. T cell compositions can 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)). The optimal dosage and treatment regime for a particular patient can readily be determined by one skilled in the art of medicine by monitoring the patient for signs of disease and adjusting the treatment accordingly. 
     In certain embodiments, it can be desired to administer activated T cells to a subject and then subsequently redraw blood (or have an apheresis performed), activate T cells therefrom, and reinfuse the patient with these activated and expanded T cells. This process can be carried out multiple times every few weeks. In certain embodiments, T cells can be activated from blood draws of from 10 cc to 400 cc. In certain embodiments, T cells are activated from blood draws of 20 cc, 30 cc, 40 cc, 50 cc, 60 cc, 70 cc, 80 cc, 90 cc, or 100 cc. Not to be bound by theory, using this multiple blood draw/multiple reinfusion protocol can serve to select out certain populations of T cells. In another embodiment, it can be desired to administer activated T cells of the subject composition following lymphodepletion of the patient, either via radiation or chemotherapy. 
     The administration of compositions described herein can be carried out in any convenient manner, including by aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation. The compositions described herein can be administered to a patient subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous (i.v.) injection, or intraperitoneally. In one embodiment, the T cell compositions of the present invention are administered to a patient by intradermal or subcutaneous injection. In another embodiment, the ROR-1 CAR-T cell compositions of the present invention are administered by i.v. injection. The compositions of T cells can be injected directly into a lymph node, or site of primary tumor or metastasis. 
     The dosage of the above treatments to be administered to a patient will vary with the precise nature of the condition being treated and the recipient of the treatment. The scaling of dosages for human administration can be performed according to art-accepted practices. For example, the dose of the above treatment can be in the range of 1×10 4  CAR+ cells/kg to 5×10 6  CAR+ cells/kg. Exemplary doses can be 1×10 2  CAR+ cells/kg, 1×10 3  CAR+ cells/kg, 1×10 4  CAR+ cells/kg, 1×10 5  CAR+ cells/kg, 3×10 5  CAR+ cells/kg, 1×10 6  CAR+ cells/kg,5×10 6  CAR+ cells/kg, 1×10 7  CAR+ cells/kg, 1×10 8  CAR+ cells/kg or 1×10 9  CAR+ cells/kg. The appropriate dose can be adjusted accordingly for an adult or a pediatric patient. 
     Alternatively, a typical amount of immune effector cells administered to a mammal (e.g., a human) can be, for example, in the range of one hundred, one thousand, ten thousand, one million to 100 billion cells; however, amounts below or above this exemplary range are within the scope of the invention. For example, the dose of inventive host cells can be about 1 million to about 50 billion cells (e.g., about 5 million cells, about 25 million cells, about 500 million cells, about 1 billion cells, about 5 billion cells, about 20 billion cells, about 30 billion cells, about 40 billion cells, or a range defined by any two of the foregoing values), about 10 million to about 100 billion cells (e.g., about 20 million cells, about 30 million cells, about 40 million cells, about 60 million cells, about 70 million cells, about 80 million cells, about 90 million cells, about 10 billion cells, about 25 billion cells, about 50 billion cells, about 75 billion cells, about 90 billion cells, or a range defined by any two of the foregoing values), about 100 million cells to about 50 billion cells (e.g., about 120 million cells, about 250 million cells, about 350 million cells, about 450 million cells, about 650 million cells, about 800 million cells, about 900 million cells, about 3 billion cells, about 30 billion cells, about 45 billion cells, or a range defined by any two of the foregoing values). 
     Therapeutic or prophylactic efficacy can be monitored by periodic assessment of treated patients. For repeated administrations over several days or longer, depending on the condition, the treatment is repeated until a desired suppression of disease symptoms occurs. However, other dosage regimens can be useful and are within the scope of the invention. The desired dosage can be delivered by a single bolus administration of the composition, by multiple bolus administrations of the composition, or by continuous infusion administration of the composition. 
     The composition comprising the immune effector cells expressing the disclosed nucleic acid sequences, or a vector comprising the those nucleic acid sequences, can be administered with one or more additional therapeutic agents, which can be co-administered to the mammal. By “co-administering” is meant administering one or more additional therapeutic agents and the composition comprising the inventive host cells or the inventive vector sufficiently close in time to enhance the effect of one or more additional therapeutic agents, or vice versa. In this regard, the composition comprising the immune effector cells described herein or a vector described herein can be administered simultaneously with one or more additional therapeutic agents, or first, and the one or more additional therapeutic agents can be administered second, or vice versa. Alternatively, the composition comprising the disclosed immune effector cells or the vectors described herein and the one or more additional therapeutic agents can be administered simultaneously. 
     An example of a therapeutic agents that can be included in or co-administered with the composition (or included in kits) comprising the inventive host cells and/or the inventive vectors are interleukins, cytokines, interferons, adjuvants and chemotherapeutic agents. In embodiments, the additional therapeutic agents are IFN-alpha, IFN-beta, IFN-gamma, GM-CSF, G-CSF, M-CSF, LT-beta, TNF-alpha, growth factors, and hGH, a ligand of human Toll-like receptor TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, and TLR10. 
     “Antifoaming agents” reduce foaming during processing which can result in coagulation of aqueous dispersions, bubbles in the finished film, or generally impair processing. Exemplary anti-foaming agents include silicon emulsions or sorbitan sesquoleate. 
     “Antioxidants” include, for example, butylated hydroxytoluene (BHT), sodium ascorbate, ascorbic acid, sodium metabisulfite and tocopherol. In certain embodiments, antioxidants enhance chemical stability where required. 
     Formulations described herein can benefit from antioxidants, metal chelating agents, thiol containing compounds and other general stabilizing agents. Examples of such stabilizing agents, include, but are not limited to: (a) about 0.5% to about 2% w/v glycerol, (b) about 0.1% to about 1% w/v methionine, (c) about 0.1% to about 2% w/v monothioglycerol, (d) about 1 mM to about 10 mM EDTA, (e) about 0.01% to about 2% w/v ascorbic acid, (f) 0.003% to about 0.02% w/v polysorbate 80, (g) 0.001% to about 0.05% w/v. polysorbate 20, (h) arginine, (i) heparin, (j) dextran sulfate, (k) cyclodextrins, (l) pentosan polysulfate and other heparinoids, (m) divalent cations such as magnesium and zinc; or (n) combinations thereof. 
     “Binders” impart cohesive qualities and include, e.g., alginic acid and salts thereof; cellulose derivatives such as carboxymethylcellulose, methylcellulose (e.g., Methocel®), hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose (e.g., Klucel®), ethylcellulose (e.g., Ethocel®), and microcrystalline cellulose (e.g., Avicel®); microcrystalline dextrose; amylose; magnesium aluminum silicate; polysaccharide acids; bentonites; gelatin; polyvinylpyrrolidone/vinyl acetate copolymer; crospovidone; povidone; starch; pregelatinized starch; tragacanth, dextrin, a sugar, such as sucrose (e.g., Dipac®), glucose, dextrose, molasses, mannitol, sorbitol, xylitol (e.g., Xylitab®), and lactose; a natural or synthetic gum such as acacia, tragacanth, ghatti gum, mucilage of isapol husks, polyvinylpyrrolidone (e.g., Polyvidone® CL, Kollidon® CL, Polyplasdone® XL-10), larch arabogalactan, Veegum®, polyethylene glycol, waxes, sodium alginate, and the like. 
     A “carrier” or “carrier materials” include any commonly used excipients in pharmaceutics and should be selected on the basis of compatibility with compounds disclosed herein, such as, compounds of ibrutinib and an anticancer agent, and the release profile properties of the desired dosage form. Exemplary carrier materials include, e.g., binders, suspending agents, disintegration agents, filling agents, surfactants, solubilizers, stabilizers, lubricants, wetting agents, diluents, and the like. “Pharmaceutically compatible carrier materials” can include, but are not limited to, acacia, gelatin, colloidal silicon dioxide, calcium glycerophosphate, calcium lactate, maltodextrin, glycerine, magnesium silicate, polyvinylpyrrollidone (PVP), cholesterol, cholesterol esters, sodium caseinate, soy lecithin, taurocholic acid, phosphotidylcholine, sodium chloride, tricalcium phosphate, dipotassium phosphate, cellulose and cellulose conjugates, sugars sodium stearoyl lactylate, carrageenan, monoglyceride, diglyceride, pregelatinized starch, and the like. See, e.g., Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington&#39;s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa. 1975; Liberman, H. A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams &amp; Wilkins 1999). 
     “Dispersing agents,” and/or “viscosity modulating agents” include materials that control the diffusion and homogeneity of a drug through liquid media or a granulation method or blend method. In some embodiments, these agents also facilitate the effectiveness of a coating or eroding matrix. Exemplary diffusion facilitators/dispersing agents include, e.g., hydrophilic polymers, electrolytes, Tween® 60 or 80, PEG, polyvinylpyrrolidone (PVP; commercially known as Plasdone®), and the carbohydrate-based dispersing agents such as, for example, hydroxypropyl celluloses (e.g., HPC, HPC-SL, and HPC-L), hydroxypropyl methylcelluloses (e.g., HPMC K100, HPMC K4M, HPMC K15M, and HPMC K100M), carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate stearate (HPMCAS), noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol (PVA), vinyl pyrrolidone/vinyl acetate copolymer (S630), 4-(1,1,3,3-tetramethylbutyl)-phenol polymer with ethylene oxide and formaldehyde (also known as tyloxapol), poloxamers (e.g., Pluronics F68®, F88®, and F108®, which are block copolymers of ethylene oxide and propylene oxide); and poloxamines (e.g., Tetronic 908®, also known as Poloxamine 908®, which is a tetrafunctional block copolymer derived from sequential addition of propylene oxide and ethylene oxide to ethylenediamine (BASF Corporation, Parsippany, N.J.)), polyvinylpyrrolidone K12, polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, or polyvinylpyrrolidone K30, polyvinylpyrrolidone/vinyl acetate copolymer (S-630), polyethylene glycol, e.g., the polyethylene glycol can have a molecular weight of about 300 to about 6000, or about 3350 to about 4000, or about 7000 to about 5400, sodium carboxymethylcellulose, methylcellulose, polysorbate-80, sodium alginate, gums, such as, e.g., gum tragacanth and gum acacia, guar gum, xanthans, including xanthan gum, sugars, cellulosics, such as, e.g., sodium carboxymethylcellulose, methylcellulose, sodium carboxymethylcellulose, polysorbate-80, sodium alginate, polyethoxylated sorbitan monolaurate, polyethoxylated sorbitan monolaurate, povidone, carbomers, polyvinyl alcohol (PVA), alginates, chitosans and combinations thereof. Plasticizers such as cellulose or triethyl cellulose can also be used as dispersing agents. Dispersing agents particularly useful in liposomal dispersions and self-emulsifying dispersions are dimyristoyl phosphatidyl choline, natural phosphatidyl choline from eggs, natural phosphatidyl glycerol from eggs, cholesterol and isopropyl myristate. 
     Combinations of one or more erosion facilitator with one or more diffusion facilitator can also be used in the present compositions. 
     The term “diluent” refers to chemical compounds that are used to dilute the compound of interest prior to delivery. Diluents can also be used to stabilize compounds because they can provide a more stable environment. Salts dissolved in buffered solutions (which also can provide pH control or maintenance) are utilized as diluents in the art, including, but not limited to a phosphate buffered saline solution. In certain embodiments, diluents increase bulk of the composition to facilitate compression or create sufficient bulk for homogenous blend for capsule filling. Such compounds include e.g., lactose, starch, mannitol, sorbitol, dextrose, microcrystalline cellulose such as Avicel®; dibasic calcium phosphate, dicalcium phosphate dihydrate; tricalcium phosphate, calcium phosphate; anhydrous lactose, spray-dried lactose; pregelatinized starch, compressible sugar, such as Di-Pac® (Amstar); mannitol, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate stearate, sucrose-based diluents, confectioner&#39;s sugar; monobasic calcium sulfate monohydrate, calcium sulfate dihydrate; calcium lactate trihydrate, dextrates; hydrolyzed cereal solids, amylose; powdered cellulose, calcium carbonate; glycine, kaolin; mannitol, sodium chloride; inositol, bentonite, and the like. 
     “Filling agents” include compounds such as lactose, calcium carbonate, calcium phosphate, dibasic calcium phosphate, calcium sulfate, microcrystalline cellulose, cellulose powder, dextrose, dextrates, dextran, starches, pregelatinized starch, sucrose, xylitol, lactitol, mannitol, sorbitol, sodium chloride, polyethylene glycol, and the like. 
     “Lubricants” and “glidants” are compounds that prevent, reduce or inhibit adhesion or friction of materials. Exemplary lubricants include, e.g., stearic acid, calcium hydroxide, talc, sodium stearyl fumerate, a hydrocarbon such as mineral oil, or hydrogenated vegetable oil such as hydrogenated soybean oil (Sterotex®), higher fatty acids and their alkali-metal and alkaline earth metal salts, such as aluminum, calcium, magnesium, zinc, stearic acid, sodium stearates, glycerol, talc, waxes, Stearowet®, boric acid, sodium benzoate, sodium acetate, sodium chloride, leucine, a polyethylene glycol (e.g., PEG-4000) or a methoxypolyethylene glycol such as Carbowax™, sodium oleate, sodium benzoate, glyceryl behenate, polyethylene glycol, magnesium or sodium lauryl sulfate, colloidal silica such as Syloid™, Cab-O-Sil®, a starch such as corn starch, silicone oil, a surfactant, and the like. 
     “Plasticizers” are compounds used to soften the microencapsulation material or film coatings to make them less brittle. Suitable plasticizers include, e.g., polyethylene glycols such as PEG 300, PEG 400, PEG 600, PEG 1450, PEG 3350, and PEG 800, stearic acid, propylene glycol, oleic acid, triethyl cellulose and triacetin. In some embodiments, plasticizers can also function as dispersing agents or wetting agents. 
     “Solubilizers” include compounds such as triacetin, triethylcitrate, ethyl oleate, ethyl caprylate, sodium lauryl sulfate, sodium doccusate, vitamin E TPGS, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, hydroxypropylmethyl cellulose, hydroxypropyl cyclodextrins, ethanol, n-butanol, isopropyl alcohol, cholesterol, bile salts, polyethylene glycol 200-600, glycofurol, transcutol, propylene glycol, and dimethyl isosorbide and the like. 
     “Stabilizers” include compounds such as any antioxidation agents, buffers, acids, preservatives and the like. 
     “Suspending agents” include compounds such as polyvinylpyrrolidone, e.g., polyvinylpyrrolidone K12, polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, or polyvinylpyrrolidone K30, vinyl pyrrolidone/vinyl acetate copolymer (S630), polyethylene glycol, e.g., the polyethylene glycol can have a molecular weight of about 300 to about 6000, or about 3350 to about 4000, or about 7000 to about 5400, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose acetate stearate, polysorbate-80, hydroxyethylcellulose, sodium alginate, gums, such as, e.g., gum tragacanth and gum acacia, guar gum, xanthans, including xanthan gum, sugars, cellulosics, such as, e.g., sodium carboxymethylcellulose, methylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, polysorbate-80, sodium alginate, polyethoxylated sorbitan monolaurate, polyethoxylated sorbitan monolaurate, povidone and the like. 
     “Surfactants” include compounds such as sodium lauryl sulfate, sodium docusate, Tween 60 or 80, triacetin, vitamin E TPGS, sorbitan monooleate, polyoxyethylene sorbitan monooleate, polysorbates, polaxomers, bile salts, glyceryl monostearate, copolymers of ethylene oxide and propylene oxide, e.g., Pluronic® (BASF), and the like. Some other surfactants include polyoxyethylene fatty acid glycerides and vegetable oils, e.g., polyoxyethylene (60) hydrogenated castor oil; and polyoxyethylene alkylethers and alkylphenyl ethers, e.g., octoxynol 10, octoxynol 40. In some embodiments, surfactants can be included to enhance physical stability or for other purposes. 
     “Viscosity enhancing agents” include, e.g., methyl cellulose, xanthan gum, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxypropylmethyl cellulose acetate stearate, hydroxypropylmethyl cellulose phthalate, carbomer, polyvinyl alcohol, alginates, acacia, chitosans and combinations thereof. 
     “Wetting agents” include compounds such as oleic acid, glyceryl monostearate, sorbitan monooleate, sorbitan monolaurate, triethanolamine oleate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monolaurate, sodium docusate, sodium oleate, sodium lauryl sulfate, sodium doccusate, triacetin, Tween 80, vitamin E TPGS, ammonium salts and the like. 
     Kits and Compositions 
     One aspect of the disclosure relates to kits and compositions including a first vector including coding regions that encode the ROR-1-specific CARs of the invention and optionally genes included for safety reasons, e.g., HER1t or HER1t-1 and functional variants thereof, or CD20 or CD20t-1, and functional variants thereof. The kits and compositions can further include cytokines. In another aspect, the kits and compositions can include RHEOSWITCH® gene switch components. These kits and compositions can include multiple vectors each encoding different proteins or subsets of proteins. These vectors can be viral, non-viral, episomal, or integrating. In some embodiments, the vectors are transposons, e.g., Sleeping Beauty transposons. 
     In some embodiments, the kits and compositions include not only vectors but also cells and agents such as interleukins, cytokines, interleukins and chemotherapeutics, adjuvants, wetting agents, or emulsifying agents. In one embodiment the cells are T cells. In one embodiment the kits and composition includes IL-2. In one embodiment, the kits and compositions include IL-21. In one embodiment, the kits and compositions include Bcl-2, STAT3 or STATS inhibitors. In embodiments, the kit includes IL-15, or mbIL-15. 
     Disclosed herein, in certain embodiments, are kits and articles of manufacture for use with one or more methods described herein. Such kits include a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) comprising one of the separate elements to be used in a method described herein. Suitable containers include, for example, bottles, vials, syringes, and test tubes. In one embodiment, the containers are formed from a variety of materials such as glass or plastic. 
     The articles of manufacture provided herein contain packaging materials. Examples of pharmaceutical packaging materials include, but are not limited to, blister packs, bottles, tubes, bags, containers, bottles, and any packaging material suitable for a selected formulation and intended mode of administration and treatment. 
     For example, the container(s) include CAR-T cells (e.g., ROR-1-specific CAR-T cells described herein), and optionally in addition with cytokines and/or chemotherapeutic agents disclosed herein. Such kits optionally include an identifying description or label or instructions relating to its use in the methods described herein. 
     A kit typically includes labels listing contents and/or instructions for use, and package inserts with instructions for use. A set of instructions will also typically be included. 
     In some embodiments, a label is on or associated with the container. In one embodiment, a label is on a container when letters, numbers or other characters forming the label are attached, molded or etched into the container itself; a label is associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. In one embodiment, a label is used to indicate that the contents are to be used for a specific therapeutic application. The label also indicates directions for use of the contents, such as in the methods described herein. 
     EXAMPLES 
     These examples are provided for illustrative purposes only and not to limit the scope of the claims provided herein. 
     Example 1 Nucleofection of T Cells with Sleeping Beauty System 
     To generate the genetically modified T cells, cryopreserved pan T cells were thawed, washed and resuspended with pre-warmed Phenol Red free RPMI 1640 media supplemented with FBS and Glutamax (R20 media) and placed in in a humidified incubator at 37° C. with 5% CO2. Cells were counted and centrifuged and resuspended in nucleofection buffer. To generate CAR− T cells, a total of 15 μg of the transposon plasmid(s) comprising CAR constructs were combined with 5 μg of plasmid encoding SB transposase for each nucleofection cuvette reaction. Electroporation of the T cells was achieved using the Amaxa 2b Nucleofection device or 4D Nucleofector (Lonza, Walkersville, Md.). Following electroporation, the contents from each cuvette were transferred to pre-warmed R20 media and placed in incubator at 37° C. A sample of each T cell culture was taken for flow cytometric analysis to characterize CAR expression where applicable at a specified time point. CAR +  T cells were numerically expanded ex vivo for further characterization. For ex vivo numerical expansion of the generated CAR+ T cells, the T cells were further co-cultured with activating and propagating cells (AaPCs). Briefly, irradiated AaPCs derived from K562 cell line engineered to express CD86, 41BBL, mbIL15 along with ROR1 antigen were co-cultured with CAR + T cells in complete media with IL-21 and IL-2 for subsequent weekly AaPC additions. 
     Flow cytometric analysis for CAR expression was performed at Day 1 after electroporation and prior to each AaPC stimulation using fluorescently labeled recombinant ROR1-Fc fusion protein, biotin labelled soluble extracellular domain of ROR1 or Protein-L labelled with AF647. Cells were gated on live CD3+ cells. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Murine ROR1 scFv CAR constructs with various signal peptides 
               
            
           
           
               
               
            
               
                 Construct No. 
                 CAR ORF 
               
               
                   
               
               
                 1 
                 mIgVH (SP)-Murine ROR1 scFv-CD8a-CD28z 
               
               
                 2 
                 IgKappa (SP)-Murine ROR1 scFv-CD8a-CD28z 
               
               
                 3 
                 CD28(SP)- Murine ROR1 scFv-CD8a-CD28z 
               
               
                 4 
                 CD8a(SP)- Murine ROR1 scFv-CD8a-CD28z 
               
               
                   
               
            
           
         
       
     
     The above mentioned CARs were constructed.  FIG. 5  demonstrates that short CD8a stalk does not permit surface expression of ROR1 CAR regardless of signal peptide utilized. Other signal peptides that were tested included GM-CSFRα, β2M, azurocidin, Human Serum Albumin (HSA), A2M receptor associated protein, IgHV3-23, IgHV3-33, and IgKV1-D33. 
     Example 2: Optimization of ROR1 CAR 
     In all approximately 120 CAR vectors were designed and built based on various permutations of signal peptides, orientation of VL and VH chain of anti-ROR1 antibody, spacers of varying lengths, transmembrane and signaling domains. For example, 15 signal peptides, 2 orientations, and 7 different spacers of varying lengths, 2 different transmembrane and signaling domains were tested in various combinations. The expression of ROR1 CAR was found to be dependent on signal peptide, orientation and stalk type length. From these, 3 CAR constructs were identified with strong surface expression. 
     CAR-T cells expressing ROR1 CARs of different spacer lengths, signal peptides, and VH-VL orientation were generated by electroporation of SB system plasmids in healthy donor PBMCs as described in Example 1. CAR-T cells were numerically expanded ex vivo by co-culture with ROR1 expressing AaPC by once weekly stimulation as described in Example 1. Expression of CAR was measured by multi parameter flow cytometry at Day 1 and Day 8 post nucleofection. CAR-T test articles evaluated are listed in Table 5. 
       FIG. 6  shows flow cytometry data on ROR1 CAR expression of different ROR1 CAR (murine scFv)-T cells with. Cells were gated on live CD3+ cells. As shown in  FIG. 6 , varying degrees of murine ROR1 CAR expression was observed one day post gene transfer depending on the spacer utilized for construction of CAR molecule. Enrichment of CAR+ T cells was observed upon co-culture of CAR+ T cells with ROR1+ AaPC line in vitro. For murine ROR1 CAR-T, better surface expression of CAR on T cells was observed using longer spacers. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 ROR1 CAR constructs as utilized in FIGS. 6-7. 
               
            
           
           
               
               
            
               
                 Construct No. 
                 CAR ORF 
               
               
                   
               
            
           
           
               
               
            
               
                 5 
                 mIgVH (SP)-Murine ROR1 scFv-CD8a-2X-CD28z 
               
               
                 6 
                 mIgVH (SP)-Murine ROR1 scFv-CD8a-3X-CD28z 
               
               
                 7 
                 mIgVH (SP)-Murine ROR1 scFv-CD8a-4X-CD28z 
               
               
                 8 
                 mIgVH (SP)-Murine ROR1 scFv-LNGFR-CD28z 
               
               
                 9 
                 hIgK(SP)- Murine ROR1 scFv-CD8a-3X-CD28z 
               
               
                 10 
                 hCD8a(SP)-Murine ROR1 scFv-CD8a-3X-CD28z 
               
               
                 11 
                 hCD28(SP) -Murine ROR1 scFv-CD8a-3X-CD28z 
               
               
                 12 
                 hβ2M (SP)-Murine ROR1 scFv-CD8a-3X-CD28z 
               
               
                 13 
                 HAS(SP) -Murine ROR1 scFv-CD8a-3X-CD28z 
               
               
                 14 
                 hAzurocidin-Murine ROR1 scFv-CD8a-3X-CD28z 
               
               
                   
               
            
           
         
       
     
       FIG. 7  demonstrates varying degrees of ROR1 CAR expression using CD8a-3X spacer and different combinations of signal peptides. As shown in  FIG. 7 , signal peptides such as mIgVH, CD8a, (32M and Azurocidin allowed for better surface expression of CAR on T cells. The different signal peptides had no effect on surface expression of ROR1 CAR when CD8a-1X spacer was used. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 C ROR1 CAR constructs as utilized in FIG. 8. 
               
            
           
           
               
               
               
            
               
                 Construct 
                   
                   
               
               
                 No. 
                 CAR ORF 
                 Orientation 
               
               
                   
               
               
                 15 
                 mgIVH(SP)-murine ROR1scFv -FcM-CD28z 
                 VL-VH 
               
               
                 16 
                 hGMCSFR- murine ROR1scFv -FcM-CD28z 
                 VL-VH 
               
               
                 17 
                 GM-CSFR(SP)-Murine ROR1 
                 VH-whitlow 
               
               
                   
                 scFv-CD8a-3X-CD28z 
                 linker-VL 
               
               
                 18 
                 IgHV3-23- Murine ROR1 
                 VL-VH 
               
               
                   
                 scFv-CD8a-3X-CD28z 
               
               
                 19 
                 IgHV3-23 (SP)- Murine ROR1 
                 VH-whitlow 
               
               
                   
                 scFv-CD8a-3X-CD28z 
                 linker-VL 
               
               
                   
               
            
           
         
       
     
       FIG. 8  demonstrates that reversing orientation from VL-VH to VH-VL enables surface expression of murine ROR1CAR from GMCSFR and IGHV3-23 signal peptides. Based on the above described data, CD8a-3X stalk was selected as a spacer, IgHV3-23 was selected as a signal peptide, with VL-VH as a preferred orientation, and CD8TM-CD28z signaling domain in the murine ROR1 CAR. 
     Example 3 Murine ROR1 CAR with CD8a-3x Stalk 
     The functional capability of murine ROR1 CAR-T cells was tested in an in vitro model. Mouse EL4 cell line was transduced to express human ROR1 on cell surface (EL4-ROR1), and secretion of IFN-γ and was measured upon co-culture of murine ROR1 scFv-CD8-3x-CD28z (CAR)+ T cells with RORY′ target cells.  FIG. 9  shows murine ROR1 CAR with CD8-3x stalk demonstrates antigen specific IFN-γ expression upon coculture with ROR+ target cells. 
     Furthermore, the capability of the ROR1 CAR-T to recognize target cells with or without ROR1 expression was assessed in CD107a degranulation assay. CD107a, also known as lysosomal-associate membrane protein-1 (LAMP-1), is constitutively expressed in the late endosomes-lysosomes of cells but transiently expressed on the cell surface on degranulating cells. As shown in  FIGS. 9A-9B , significant expression of CD107a degranulation was observed upon coculture with EL4-ROR1 cell line while effector cells only and coculture with EL4 cell line had minimal degranulation observed. 
     Example 4 Humanization of ROR1 scFv 
     To reduce immunogenicity of murine ROR1 scFv and to prevent immune-mediated CAR T cell deletion in vivo, efforts were undertaken to humanize the murine ROR1 scFv. 
     A total of 168 humanized ROR1 scFvs were designed based on the sequence of murine ROR1 scFv and tested. 77 of the humanized antibody clones were successfully expressed. Out of the 77 humanized clones, 42 retained the ability to bind ROR1 antigen. 21 clones were further selected for affinity maturation. 10 humanized antibodies showed binding affinities ≤2.0 nM in IgG format. Additional scFv variants based on combination of different humanized VH and VL chains were also designed and tested. 
     Binding affinity of various humanized ROR1 scFv clones were assessed by surface plasmon resonance (SPR) assay using Biacore 3000. Variable regions of humanized ROR1 antibodies were fused to mouse constant chain regions to generate chimeric mouse IgG1 mAbs. Extracellular domain (ECD) of ROR1 fused to human Fc region was immobilized on sensor chip CMS. Different concentrations of humanized antibodies were injected in solution phase and data was analyzed using BIAevaluation to calculate Kd of the antibodies. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Binding affinity of humanized clones of murine ROR1 scFv 
               
            
           
           
               
               
               
            
               
                   
                 Humanized clones 
                 Affinity (Kd) 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Clone 04 
                 ~55 
                 nM 
               
               
                   
                 Clone 05 
                 ~35 
                 nM 
               
               
                   
                 Clone 07 
                 ~90 
                 nM 
               
               
                   
                 Clone 14 
                 1.45 
                 nM 
               
               
                   
                 Clone 16 
                 3.03 
                 nM 
               
               
                   
                 Clone 18 
                 12.7 
                 nM 
               
               
                   
                 Hum ROR1_14VH_(G4S)3x_VL_16 
                 131 
                 nM 
               
            
           
           
               
               
               
            
               
                   
                 Hum ROR1_05VH_(G4S)3x_VL_14 
                 3.55E−10M 
               
               
                   
                 Hum ROR1_05VH_(G4S)3x_VL_16 
                 3.37E−10M 
               
               
                   
                 Hum ROR1_07VH_(G4S)3x_VL_05 
                 7.16E−09M 
               
               
                   
                 Hum ROR1_07VH_(G4S)3x_VL_16 
                 4.08E−09M 
               
               
                   
                 Hum ROR1_07VH_(G4S)3x_VL_18 
                 1.17E−08M 
               
               
                   
                 Hum ROR1_18VH_(G4S)3x_VL_04 
                 3.72E−10M 
               
               
                   
                 Hum ROR1_18VH_(G4S)3x_VL_07 
                 3.87E−09M 
               
               
                   
                 Hum ROR1_18VH_(G4S)3x_VL_14 
                 2.09E−10M 
               
               
                   
                 Hum ROR1_18VH_(G4S)3x_VL_16 
                 1.60E−09M 
               
               
                   
                 Hum_design_14_variant3 
                  1.3E−09M 
               
               
                   
                 Hum_design_14_variant4 
                 4.08E−10M 
               
               
                   
                 Hum_design_14_variant5 
                 4.52E−09M 
               
               
                   
                   
               
            
           
         
       
     
     Based on top candidates from the humanization campaign, the following CAR constructs were designed and tested. 
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Humanized ROR1 CAR constructs as utilized in 
               
               
                 FIGS. 10A-10B, FIG. 11, FIG. 12 and Table 9. 
               
            
           
           
               
               
            
               
                 Construct No. 
                 CAR ORF 
               
               
                   
               
               
                 20 
                 MurineROR1_v2 (VL-VH). CD8a(3x).CD28z 
               
               
                 21 
                 IGVH3-33sp. hROR1(VH-VL)_14.CD8a(3x).CD28z 
               
               
                 22 
                 mIgVH3 sp. hROR1 (VH-VL)_14. CD8a(3x).CD28z 
               
               
                 23 
                 hROR1(VL-VH)_05.CD8a(3x).CD28z 
               
               
                 24 
                 hROR1(VH-VL)_14-3.CD8a(3x).CD28z 
               
               
                 25 
                 hROR1(VH-VL)_14-4.CD8a(3x).CD28z 
               
               
                 26 
                 hROR1(VH_5-VL_14).CD8a(3x).CD28z 
               
               
                 27 
                 hROR1(VH_5-VL_16).CD8a(3x).CD28z 
               
               
                 28 
                 hROR1(VH_18-VL_04).CD8a(3x).CD28z 
               
               
                 29 
                 hROR1(VH_18-VL_14).CD8a(3x).CD28z 
               
               
                 30 
                 Mock transfected T cells 
               
               
                   
               
            
           
         
       
     
     JeKo-1 tumor cells expressing fFLUC (0.5×10 6  cells) were administered IP into NSG mice on Day 0. On Day 8, mice with established tumor burden (as confirmed by IVIS imaging) were randomized to receive a single IV injection with either: Saline (HBSS), or T cells transfected with CAR constructs as described above. CAR-T cells were numerically expanded by 2x weekly stimulations ex vivo by coculture with ROR1+ AaPC. Effectiveness against tumor growth was evaluated by in vivo bioluminescence (IVIS) imaging performed every 7 days and 36 days post CAR-T cell dosing to assess tumor burden ( FIGS. 10A, 10B and 11 ). Whole blood samples in EDTA were collected once per week and subjected to multi-parameter flow cytometry for evaluation of humanized ROR1 CAR T cell persistence ( FIG. 12 ), expansion and determination of the different T cell subsets. 
     A lead humanized ROR1 CAR (hROR1(VH_5-VL_14).CD8a(3x).CD28z) was selected based on similarity to the murine ROR1 CAR in scFv affinity, ROR1-Fc binding, CAR expression, CAR T-cell expression, in vitro ROR-1 specific cytokine production, in vitro ROR-1 specific cytotoxicity and in vivo ROR-1 anti-tumor activity. 
     A summary of the data is provided in Table 9 below. 
                     TABLE 9                  Summary of Constructs tested.                             In vivo                                             ROR1-His   ROR1-Fc   Tumor       In vitro                                                         Affinity   Affinity   growth   CD8 in   ROR1-CAR in   ROR1-FC                   Construct #   (KD, M)   (KD, M)   inhibition   circulation   circulation   binding   Cytotoxicity   Cytokines   Expansion               20   7.07E−08   2.31E−08   2   1   2   3   3   3   3       21   1.45E−09   ND   2   1   1   2   3   3   3       22   1.45E−09   ND   2   2   2   2   3   3   3       23   3.74E−08   3.50E−08   1   1   1   2   3   3   3       24   1.30E−09   9.59E−10   2   2   1   2   3   3   3       25   4.08E−10   2.84E−10   1   3   2   3   2   3   3       26   3.55E−10   1.93E−10   3   3   3   3   3   3   3       27   3.37E−10   2.73E−10   0   2   0   0   0   3   3       28   3.72E−10   2.71E−10   1   1   1   2   3   3   3       29   2.09E−10   2.01E−10   3   1   1   3   3   3   3               ND—not determined            
Relative performance score from 0 to 3 with 0 being worst and 3 being the best performance
 
     Example 5 In Vitro and In Vivo Experiments 
     Various DNA plasmids expressing a SB transposon system, i.e. SB11, membrane bound IL-15 (mbIL-15), cell tag and lead chimeric antigen receptor (CAR), were transfected into peripheral blood mononuclear cells (PBMC) via nucleofection to redirect T cell specificity. Constitutive expression of mbIL-15 or ligand inducible expression of mbIL-15 in combination with constitutive expression of lead ROR1 CAR was examined as described in Table 10. 
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Combination of Transposons as utilized in FIGS. 13A-13B. 
               
            
           
           
               
               
               
            
               
                 Combination No. 
                 Transposon #1 
                 Transposon #2 
               
               
                   
               
               
                 1 
                 Constitutive CAR 
                 Constitutive 
               
               
                   
                 (FIG. 1C) 
                 mbIL-15.HER1t 
               
               
                   
                   
                 (FIG. 1E) 
               
               
                 2 
                 Constitutive 
                 Constitutive 
               
               
                   
                 CAR.HER1t 
                 mbIL-15.HER1t 
               
               
                   
                 (FIG. 1D) 
                 (FIG. 1E) 
               
               
                 3 
                 Constitutive CAR.HER1t. 
                 Gene Switch components 
               
               
                   
                 Inducible mbIL-15.HER1t 
                 (FIG. 2E) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Summary of combinations tested. 
               
            
           
           
               
               
               
               
               
            
               
                   
                 Combination 
                 1 
                 2 
                 3 
               
               
                   
                   
               
               
                   
                 CAR 
                 hROR1 
                 hROR1 
                 hROR1 
               
               
                   
                 mbIL-15 
                 const 
                 const. 
                 RTS ® 
               
               
                   
                 Expansion 
                 ++ 
                 + 
                 + 
               
               
                   
                 CAR+ % 
                 +++ 
                 + 
                 ++ 
               
               
                   
                 mbIL-15 (%) 
                 + 
                 + 
                 ++ 
               
               
                   
                 CD107 
                 ++ 
                 +/− 
                 + 
               
               
                   
                 IFN-γ 
                 ++ 
                 +/− 
                 + 
               
               
                   
                 TNF-α 
                 + 
                 − 
                 +/− 
               
               
                   
                   
               
               
                   
                 Relative performance score from − to +++, ‘−’ being undetectable performance and +++ being the best performance. 
               
            
           
         
       
     
     RTS-mbIL-15 in combination with hROR1 CAR was further tested in vitro using SKOV3_fLUC ( FIG. 13A ) and JeKo1_fLUC ( FIG. 13B ) tumor cell lines. As before, the 3 combinations of SB transposons encoding for hROR1 CAR and mbIL-15 were electroporated in healthy donor T cells. CAR+T cells were numerically expanded ex vivo by co-culture with ROR1 expressing AaPC by once weekly stimulation as previously described for 2X stimulation. For ligand inducible mbIL-15 hROR1 CAR, the T cells were incubated in complete media containing IL-21 and IL-2 at following 2X stimulation of the cells. Two days after, the hROR1 CAR T cells were incubated in a cytokine free complete media and treated with veledimex or DMSO overnight. The next day, cells were counted and the frequency of ROR1 expressing T cells was estimated. T cells were then normalized for CAR expression. 
     For T cells constitutively expressing hROR1 CAR and mbIL-15, following ex vivo expansion using two weekly stimulations by coculture with AaPC, cells were cultured for an additional 3 days and counted. As before, T cells were normalized for CAR expression. 
     hROR1 CAR T cells were then mixed with each tumor cell line at different ratios: 4:1, 2:1, 0.5:1 and 0.25:1. 72 hours later, cells were removed from the incubator and pelleted. Supernatant was collected to measure cytokine production, and cell pellet was treated with OneGlo reagent for Luciferase assay.  FIGS. 13A-13B  demonstrates that ROR1+ tumor cell lines were equally killed by hROR1 CART cells with constitutive or RTS-mbIL-15 in vitro. 
     An in vivo study was conducted in mice treated with hROR-1 CAR T cells with RTS-mbIL-15. As before, JeKo-1 tumor cells (10×10 6  cells) were administered IP into NSG mice on Day 0. On Day 8, mice with established tumor burden (as confirmed by IVIS imaging) were randomized to receive a single IP injection with either: Saline (HBSS), or hROR-1 CAR T cells with RTS-mbIL-15 (+/−veledimex). Effectiveness against tumor growth was evaluated by in vivo bioluminescence (IVIS) imaging performed at specific time points post CAR-T cell dosing to assess tumor burden ( FIG. 14 ). Whole blood samples in EDTA were collected once per week and subjected to multi-parameter flow cytometry for evaluation of humanized ROR1 CAR T cell persistence, expansion and determination of the different T cell subsets. 
       FIG. 14  demonstrates that huROR1 RTS CART promotes an anti-tumor effect in a JEKO-1 xenograft mouse model in a dose-dependent manner. 
     Unless defined otherwise, all technical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of this invention. 
     While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the present disclosure. It should be understood that various alternatives to the embodiments described herein, or combinations of one or more of these embodiments or aspects described therein can be employed in practicing the present disclosure. It is intended that the following claims define the scope of the present disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby. 
     Sequences 
     Provided in Table 12 is a representative list of certain sequences included in embodiments provided herein. 
     
       
         
           
               
             
               
                 TABLE 12 
               
               
                   
               
               
                 Exemplary Sequences 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 SEQ 
                   
                 SEQ 
                   
               
               
                 Name 
                 ID NO 
                 Amino Acid Sequence 
                 ID NO 
                 Nucleotide Sequence 
               
               
                   
               
            
           
           
               
            
               
                 CAR Sequences 
               
            
           
           
               
               
               
               
               
            
               
                 Human 
                 1 
                 PLLALLAALLLAARG 
                 148 
                 ATGCACCGGCCGCGCCGCCGCGGGACG 
               
               
                 ROR1 
                   
                 AAAQETELSVSAELV 
                   
                 CGCCCGCCGCTCCTGGCGCTGCTGGCC 
               
               
                   
                   
                 PTSSWNISSELNKDSY 
                   
                 GCGCTGCTGCTGGCCGCACGCGGGGCT 
               
               
                   
                   
                 LTLDEPMNNITTSLGQ 
                   
                 GCTGCCCAAGAAACAGAGCTGTCAGTC 
               
               
                   
                   
                 TAELHCKVSGNPPPTI 
                   
                 AGTGCTGAATTAGTGCCTACCTCATCA 
               
               
                   
                   
                 RWFKNDAPVVQEPR 
                   
                 TGGAACATCTCAAGTGAACTCAACAAA 
               
               
                   
                   
                 RLSFRSTIYGSRLRIRN 
                   
                 GATTCTTACCTGACCCTCGATGAACCA 
               
               
                   
                   
                 LDTTDTGYFQCVATN 
                   
                 ATGAATAACATCACCACGTCTCTGGGC 
               
               
                   
                   
                 GKEVVSSTGVLFVKF 
                   
                 CAGACAGCAGAACTGCACTGCAAAGTC 
               
               
                   
                   
                 GPPPTASPGYSDEYEE 
                   
                 TCTGGGAATCCACCTCCCACCATCCGC 
               
               
                   
                   
                 DGFCQPYRGIACARFI 
                   
                 TGGTTCAAAAATGATGCTCCTGTGGTC 
               
               
                   
                   
                 GNRTVYMESLHMQG 
                   
                 CAGGAGCCCCGGAGGCTCTCCTTTCGG 
               
               
                   
                   
                 EIENQITAAFTMIGTSS 
                   
                 TCCACCATCTATGGCTCTCGGCTGCGG 
               
               
                   
                   
                 HLSDKCSQFAIPSLCH 
                   
                 ATTAGAAACCTCGACACCACAGACACA 
               
               
                   
                   
                 YAFPYCDETSSVPKPR 
                   
                 GGCTACTTCCAGTGCGTGGCAACAAAC 
               
               
                   
                   
                 DLCRDECEILENVLC 
                   
                 GGCAAGGAGGTGGTTTCTTCCACTGGA 
               
               
                   
                   
                 QTEYIFARSNPMILMR 
                   
                 GTCTTGTTTGTCAAGTTTGGCCCCCCTC 
               
               
                   
                   
                 LKLPNCEDLPQPESPE 
                   
                 CCACTGCAAGTCCAGGATACTCAGATG 
               
               
                   
                   
                 AANCIRIGIPMADPIN 
                   
                 AGTATGAAGAAGATGGATTCTGTCAGC 
               
               
                   
                   
                 KNHKCYNSTGVDYR 
                   
                 CATACAGAGGGATTGCATGTGCAAGAT 
               
               
                   
                   
                 GTVSVTKSGRQCQPW 
                   
                 TTATTGGCAACCGCACCGTCTATATGG 
               
               
                   
                   
                 NSQYPHTHTFTALRFP 
                   
                 AGTCTTTGCACATGCAAGGGGAAATAG 
               
               
                   
                   
                 ELNGGHSYCRNPGNQ 
                   
                 AAAATCAGATCACAGCTGCCTTCACTA 
               
               
                   
                   
                 KEAPWCFTLDENFKS 
                   
                 TGATTGGCACTTCCAGTCACTTATCTGA 
               
               
                   
                   
                 DLCDIPACDSKDSKE 
                   
                 TAAGTGTTCTCAGTTCGCCATTCCTTCC 
               
               
                   
                   
                 KNKMEILYILVPSVAI 
                   
                 CTGTGCCACTATGCCTTCCCGTACTGCG 
               
               
                   
                   
                 PLAIALLFFFICVCRN 
                   
                 ATGAAACTTCATCCGTCCCAAAGCCCC 
               
               
                   
                   
                 NQKSSSAPVQRQPKH 
                   
                 GTGACTTGTGTCGCGATGAATGTGAAA 
               
               
                   
                   
                 VRGQNVEMSMLNAY 
                   
                 TCCTGGAGAATGTCCTGTGTCAAACAG 
               
               
                   
                   
                 KPKSKAKELPLSAVR 
                   
                 AGTACATTTTTGCAAGATCAAATCCCA 
               
               
                   
                   
                 FMEELGECAFGKIYK 
                   
                 TGATTCTGATGAGGCTGAAACTGCCAA 
               
               
                   
                   
                 GHLYLPGMDHAQLV 
                   
                 ACTGTGAAGATCTCCCCCAGCCAGAGA 
               
               
                   
                   
                 AIKTLKDYNNPQQWT 
                   
                 GCCCAGAAGCTGCGAACTGTATCCGGA 
               
               
                   
                   
                 EFQQEASLMAELHHP 
                   
                 TTGGAATTCCCATGGCAGATCCTATAA 
               
               
                   
                   
                 NIVCLLGAVTQEQPV 
                   
                 ATAAAAATCACAAGTGTTATAACAGCA 
               
               
                   
                   
                 CMLFEYINQGDLHEF 
                   
                 CAGGTGTGGACTACCGGGGGACCGTCA 
               
               
                   
                   
                 LIMRSPHSDVGCSSDE 
                   
                 GTGTGACCAAATCAGGGCGCCAGTGCC 
               
               
                   
                   
                 DGTVKSSLDHGDFLH 
                   
                 AGCCATGGAATTCCCAGTATCCCCACA 
               
               
                   
                   
                 IAIQIAAGMEYLSSHF 
                   
                 CACACACTTTCACCGCCCTTCGTTTCCC 
               
               
                   
                   
                 FVHKDLAARNILIGEQ 
                   
                 AGAGCTGAATGGAGGCCATTCCTACTG 
               
               
                   
                   
                 LHVKISDLGLSREIYS 
                   
                 CCGCAACCCAGGGAATCAAAAGGAAG 
               
               
                   
                   
                 ADYYRVQSKSLLPIR 
                   
                 CTCCCTGGTGCTTCACCTTGGATGAAA 
               
               
                   
                   
                 WMPPEAIMYGKFSSD 
                   
                 ACTTTAAGTCTGATCTGTGTGACATCCC 
               
               
                   
                   
                 SDIWSFGVVLWEIFSF 
                   
                 AGCGTGCGATTCAAAGGATTCCAAGGA 
               
               
                   
                   
                 GLQPYYGFSNQEVIE 
                   
                 GAAGAATAAAATGGAAATCCTGTACAT 
               
               
                   
                   
                 MVRKRQLLPCSEDCP 
                   
                 ACTAGTGCCAAGTGTGGCCATTCCCCT 
               
               
                   
                   
                 PRMYSLMTECWNEIP 
                   
                 GGCCATTGCTTTACTCTTCTTCTTCATT 
               
               
                   
                   
                 SRRPRFKDIHVRLRS 
                   
                 TGCGTCTGTCGGAATAACCAGAAGTCA 
               
               
                   
                   
                 WEGLSSHTSSTTPSGG 
                   
                 TCGTCGGCACCAGTCCAGAGGCAACCA 
               
               
                   
                   
                 NATTQTTSLSASPVSN 
                   
                 AAACACGTCAGAGGTCAAAATGTAGA 
               
               
                   
                   
                 LSNPRYPNYMFPSQGI 
                   
                 GATGTCAATGCTGAATGCATATAAACC 
               
               
                   
                   
                 TPQGQIAGFIGPPIPQN 
                   
                 CAAGAGCAAGGCTAAAGAGCTACCTCT 
               
               
                   
                   
                 QRFIPINGYPIPPGYAA 
                   
                 TTCTGCTGTACGCTTTATGGAAGAATT 
               
               
                   
                   
                 FPAAHYQPTGPPRVIQ 
                   
                 GGGTGAGTGTGCCTTTGGAAAAATCTA 
               
               
                   
                   
                 HCPPPKSRSPSSASGS 
                   
                 TAAAGGCCATCTCTATCTCCCAGGCAT 
               
               
                   
                   
                 TSTGHVTSLPSSGSNQ 
                   
                 GGACCATGCTCAGCTGGTTGCTATCAA 
               
               
                   
                   
                 EANIPLLPHMSIPNHP 
                   
                 GACCTTGAAAGACTATAACAACCCCCA 
               
               
                   
                   
                 GGMGITVFGNKSQKP 
                   
                 GCAATGGACGGAATTTCAACAAGAAG 
               
               
                   
                   
                 YKIDSKQASLLGDANI 
                   
                 CCTCCCTAATGGCAGAACTGCACCACC 
               
               
                   
                   
                 HGHTESMISAEL 
                   
                 CCAATATTGTCTGCCTTCTAGGTGCCGT 
               
               
                   
                   
                   
                   
                 CACTCAGGAACAACCTGTGTGCATGCT 
               
               
                   
                   
                   
                   
                 TTTTGAGTATATTAATCAGGGGGATCT 
               
               
                   
                   
                   
                   
                 CCATGAGTTCCTCATCATGAGATCCCC 
               
               
                   
                   
                   
                   
                 ACACTCTGATGTTGGCTGCAGCAGTGA 
               
               
                   
                   
                   
                   
                 TGAAGATGGGACTGTGAAATCCAGCCT 
               
               
                   
                   
                   
                   
                 GGACCACGGAGATTTTCTGCACATTGC 
               
               
                   
                   
                   
                   
                 AATTCAGATTGCAGCTGGCATGGAATA 
               
               
                   
                   
                   
                   
                 CCTGTCTAGTCACTTCTTTGTCCACAAG 
               
               
                   
                   
                   
                   
                 GACCTTGCAGCTCGCAATATTTTAATC 
               
               
                   
                   
                   
                   
                 GGAGAGCAACTTCATGTAAAGATTTCA 
               
               
                   
                   
                   
                   
                 GACTTGGGGCTTTCCAGAGAAATTTAC 
               
               
                   
                   
                   
                   
                 TCCGCTGATTACTACAGGGTCCAGAGT 
               
               
                   
                   
                   
                   
                 AAGTCCTTGCTGCCCATTCGCTGGATG 
               
               
                   
                   
                   
                   
                 CCCCCTGAAGCCATCATGTATGGCAAA 
               
               
                   
                   
                   
                   
                 TTCTCTTCTGATTCAGATATCTGGTCCT 
               
               
                   
                   
                   
                   
                 TTGGGGTTGTCTTGTGGGAGATTTTCA 
               
               
                   
                   
                   
                   
                 GTTTTGGACTCCAGCCATATTATGGATT 
               
               
                   
                   
                   
                   
                 CAGTAACCAGGAAGTGATTGAGATGGT 
               
               
                   
                   
                   
                   
                 GAGAAAACGGCAGCTCTTACCATGCTC 
               
               
                   
                   
                   
                   
                 TGAAGACTGCCCACCCAGAATGTACAG 
               
               
                   
                   
                   
                   
                 CCTCATGACAGAGTGCTGGAATGAGAT 
               
               
                   
                   
                   
                   
                 TCCTTCTAGGAGACCAAGATTTAAAGA 
               
               
                   
                   
                   
                   
                 TATTCACGTCCGGCTTCGGTCCTGGGA 
               
               
                   
                   
                   
                   
                 GGGACTCTCAAGTCACACAAGCTCTAC 
               
               
                   
                   
                   
                   
                 TACTCCTTCAGGGGGAAATGCCACCAC 
               
               
                   
                   
                   
                   
                 ACAGACAACCTCCCTCAGTGCCAGCCC 
               
               
                   
                   
                   
                   
                 AGTGAGTAATCTCAGTAACCCCAGATA 
               
               
                   
                   
                   
                   
                 TCCTAATTACATGTTCCCGAGCCAGGG 
               
               
                   
                   
                   
                   
                 TATTACACCACAGGGCCAGATTGCTGG 
               
               
                   
                   
                   
                   
                 TTTCATTGGCCCGCCAATACCTCAGAA 
               
               
                   
                   
                   
                   
                 CCAGCGATTCATTCCCATCAATGGATA 
               
               
                   
                   
                   
                   
                 CCCAATACCTCCTGGATATGCAGCGTT 
               
               
                   
                   
                   
                   
                 TCCAGCTGCCCACTACCAGCCAACAGG 
               
               
                   
                   
                   
                   
                 TCCTCCCAGAGTGATTCAGCACTGCCC 
               
               
                   
                   
                   
                   
                 ACCTCCCAAGAGTCGGTCCCCAAGCAG 
               
               
                   
                   
                   
                   
                 TGCCAGTGGGTCGACTAGCACTGGCCA 
               
               
                   
                   
                   
                   
                 TGTGACTAGCTTGCCCTCATCAGGATC 
               
               
                   
                   
                   
                   
                 CAATCAGGAAGCAAATATTCCTTTACT 
               
               
                   
                   
                   
                   
                 ACCACACATGTCAATTCCAAATCATCC 
               
               
                   
                   
                   
                   
                 TGGTGGAATGGGTATCACCGTTTTTGG 
               
               
                   
                   
                   
                   
                 CAACAAATCTCAAAAACCCTACAAAAT 
               
               
                   
                   
                   
                   
                 TGACTCAAAGCAAGCATCTTTACTAGG 
               
               
                   
                   
                   
                   
                 AGACGCCAATATTCATGGACACACCGA 
               
               
                   
                   
                   
                   
                 ATCTATGATTTCTGCAGAACTG 
               
               
                   
               
               
                 Human 
                 2 
                 MHRPRRRGTRPPLLA 
                 149 
                 ATGCACCGGCCGCGCCGCCGCGGGACG 
               
               
                 ROR1 
                   
                 LLAALLLAARGAAAQ 
                   
                 CGCCCGCCGCTCCTGGCGCTGCTGGCC 
               
               
                 (1-437) 
                   
                 ETELSVSAELVPTSSW 
                   
                 GCGCTGCTGCTGGCCGCACGCGGGGCT 
               
               
                   
                   
                 NISSELNKDSYLTLDE 
                   
                 GCTGCCCAAGAAACAGAGCTGTCAGTC 
               
               
                   
                   
                 PMNNITTSLGQTAEL 
                   
                 AGTGCTGAATTAGTGCCTACCTCATCA 
               
               
                   
                   
                 HCKVSGNPPPTIRWF 
                   
                 TGGAACATCTCAAGTGAACTCAACAAA 
               
               
                   
                   
                 KNDAPVVQEPRRLSF 
                   
                 GATTCTTACCTGACCCTCGATGAACCA 
               
               
                   
                   
                 RSTIYGSRLRIRNLDT 
                   
                 ATGAATAACATCACCACGTCTCTGGGC 
               
               
                   
                   
                 TDTGYFQCVATNGKE 
                   
                 CAGACAGCAGAACTGCACTGCAAAGTC 
               
               
                   
                   
                 VVSSTGVLFVKFGPPP 
                   
                 TCTGGGAATCCACCTCCCACCATCCGC 
               
               
                   
                   
                 TASPGYSDEYEEDGF 
                   
                 TGGTTCAAAAATGATGCTCCTGTGGTC 
               
               
                   
                   
                 CQPYRGIACARFIGNR 
                   
                 CAGGAGCCCCGGAGGCTCTCCTTTCGG 
               
               
                   
                   
                 TVYMESLHMQGEIEN 
                   
                 TCCACCATCTATGGCTCTCGGCTGCGG 
               
               
                   
                   
                 QITAAFTMIGTSSHLS 
                   
                 ATTAGAAACCTCGACACCACAGACACA 
               
               
                   
                   
                 DKCSQFAIPSLCHYAF 
                   
                 GGCTACTTCCAGTGCGTGGCAACAAAC 
               
               
                   
                   
                 PYCDETSSVPKPRDLC 
                   
                 GGCAAGGAGGTGGTTTCTTCCACTGGA 
               
               
                   
                   
                 RDECEILENVLCQTEY 
                   
                 GTCTTGTTTGTCAAGTTTGGCCCCCCTC 
               
               
                   
                   
                 IFARSNPMILMRLKLP 
                   
                 CCACTGCAAGTCCAGGATACTCAGATG 
               
               
                   
                   
                 NCEDLPQPESPEAAN 
                   
                 AGTATGAAGAAGATGGATTCTGTCAGC 
               
               
                   
                   
                 CIRIGIPMADPINKNH 
                   
                 CATACAGAGGGATTGCATGTGCAAGAT 
               
               
                   
                   
                 KCYNSTGVDYRGTVS 
                   
                 TTATTGGCAACCGCACCGTCTATATGG 
               
               
                   
                   
                 VTKSGRQCQPWNSQ 
                   
                 AGTCTTTGCACATGCAAGGGGAAATAG 
               
               
                   
                   
                 YPHTHTFTALRFPELN 
                   
                 AAAATCAGATCACAGCTGCCTTCACTA 
               
               
                   
                   
                 GGHSYCRNPGNQKE 
                   
                 TGATTGGCACTTCCAGTCACTTATCTGA 
               
               
                   
                   
                 APWCFTLDENFKSDL 
                   
                 TAAGTGTTCTCAGTTCGCCATTCCTTCC 
               
               
                   
                   
                 CDIPACDSKDSKEKN 
                   
                 CTGTGCCACTATGCCTTCCCGTACTGCG 
               
               
                   
                   
                 KMEILYILVPSVAIPL 
                   
                 ATGAAACTTCATCCGTCCCAAAGCCCC 
               
               
                   
                   
                 AIALLFFFICVCRNNQ 
                   
                 GTGACTTGTGTCGCGATGAATGTGAAA 
               
               
                   
                   
                 KSSSA 
                   
                 TCCTGGAGAATGTCCTGTGTCAAACAG 
               
               
                   
                   
                   
                   
                 AGTACATTTTTGCAAGATCAAATCCCA 
               
               
                   
                   
                   
                   
                 TGATTCTGATGAGGCTGAAACTGCCAA 
               
               
                   
                   
                   
                   
                 ACTGTGAAGATCTCCCCCAGCCAGAGA 
               
               
                   
                   
                   
                   
                 GCCCAGAAGCTGCGAACTGTATCCGGA 
               
               
                   
                   
                   
                   
                 TTGGAATTCCCATGGCAGATCCTATAA 
               
               
                   
                   
                   
                   
                 ATAAAAATCACAAGTGTTATAACAGCA 
               
               
                   
                   
                   
                   
                 CAGGTGTGGACTACCGGGGGACCGTCA 
               
               
                   
                   
                   
                   
                 GTGTGACCAAATCAGGGCGCCAGTGCC 
               
               
                   
                   
                   
                   
                 AGCCATGGAATTCCCAGTATCCCCACA 
               
               
                   
                   
                   
                   
                 CACACACTTTCACCGCCCTTCGTTTCCC 
               
               
                   
                   
                   
                   
                 AGAGCTGAATGGAGGCCATTCCTACTG 
               
               
                   
                   
                   
                   
                 CCGCAACCCAGGGAATCAAAAGGAAG 
               
               
                   
                   
                   
                   
                 CTCCCTGGTGCTTCACCTTGGATGAAA 
               
               
                   
                   
                   
                   
                 ACTTTAAGTCTGATCTGTGTGACATCCC 
               
               
                   
                   
                   
                   
                 AGCGTGCGATTCAAAGGATTCCAAGGA 
               
               
                   
                   
                   
                   
                 GAAGAATAAAATGGAAATCCTGTACAT 
               
               
                   
                   
                   
                   
                 ACTAGTGCCAAGTGTGGCCATTCCCCT 
               
               
                   
                   
                   
                   
                 GGCCATTGCTTTACTCTTCTTCTTCATT 
               
               
                   
                   
                   
                   
                 TGCGTCTGTCGGAATAACCAGAAGTCA 
               
               
                   
                   
                   
                   
                 TCGTCGGCA 
               
               
                   
               
               
                 Murine ROR-1 
                 3 
                 DIKMTQSPSSMYASL 
                 150 
                 GACATCAAGATGACCCAGAGCCCCAGC 
               
               
                 (VL-VH).IgG4 
                   
                 GERVTITCKASPDINS 
                   
                 TCTATGTACGCCAGCCTGGGCGAGCGC 
               
               
                 Fc-CD28m-Z 
                   
                 YLSWFQQKPGKSPKT 
                   
                 GTGACCATCACATGCAAGGCCAGCCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACAGCTACCTGTCCTGGTTC 
               
               
                   
                   
                 FSGGGSGQDYSLTINS 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 LEYEDMGIYYCLQYD 
                   
                 GACCCTGATCTACCGGGCCAACCGGCT 
               
               
                   
                   
                 EFPYTFGGGTKLEMK 
                   
                 GGTGGACGGCGTGCCAAGCAGATTTTC 
               
               
                   
                   
                 GSTSGSGKPGSGEGST 
                   
                 CGGCGGAGGCAGCGGCCAGGACTACA 
               
               
                   
                   
                 KGEVKLVESGGGLVK 
                   
                 GCCTGACCATCAACAGCCTGGAATACG 
               
               
                   
                   
                 PGGSLKLSCAASGFTF 
                   
                 AGGACATGGGCATCTACTACTGCCTGC 
               
               
                   
                   
                 SSYAMSWVRQIPEKR 
                   
                 AGTACGACGAGTTCCCCTACACCTTCG 
               
               
                   
                   
                 LEWVASISRGGTTYY 
                   
                 GAGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
                   
                 PDSVKGRFTISRDNVR 
                   
                 GGCAGCACCTCCGGCAGCGGCAAGCCT 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GGCAGCGGCGAGGGCAGCACCAAGGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 CGAAGTGAAGCTGGTGGAAAGCGGCG 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 GAGGCCTGGTGAAACCTGGCGGCAGCC 
               
               
                   
                   
                 ESKYGPPCPPCPAPEF 
                   
                 TGAAGCTGAGCTGCGCCGCCAGCGGCT 
               
               
                   
                   
                 EGGPSVFLFPPKPKDT 
                   
                 TCACCTTCAGCAGCTACGCCATGAGCT 
               
               
                   
                   
                 LMISRTPEVTCVVVD 
                   
                 GGGTCCGACAGATCCCCGAGAAGCGG 
               
               
                   
                   
                 VSQEDPEVQFNWYV 
                   
                 CTGGAATGGGTGGCCAGCATCAGCAGG 
               
               
                   
                   
                 DGVEVHNAKTKPREE 
                   
                 GGCGGCACCACCTACTACCCCGACAGC 
               
               
                   
                   
                 QFQSTYRVVSVLTVL 
                   
                 GTGAAGGGCCGGTTCACCATCAGCCGG 
               
               
                   
                   
                 HQDWLNGKEYKCKV 
                   
                 GACAACGTGCGGAACATCCTGTACCTG 
               
               
                   
                   
                 SNKGLPSSIEKTISKA 
                   
                 CAGATGAGCAGCCTGCGGAGCGAGGA 
               
               
                   
                   
                 KGQPREPQVYTLPPS 
                   
                 CACCGCCATGTACTACTGCGGCAGATA 
               
               
                   
                   
                 QEEMTKNQVSLTCLV 
                   
                 CGACTACGACGGCTACTACGCCATGGA 
               
               
                   
                   
                 KGFYPSDIAVEWESN 
                   
                 TTACTGGGGCCAGGGCACCAGCGTGAC 
               
               
                   
                   
                 GQPENNYKTTPPVLD 
                   
                 CGTGTCTAGCGAGAGCAAGTACGGCCC 
               
               
                   
                   
                 SDGSFFLYSRLTVDKS 
                   
                 TCCCTGCCCCCCTTGCCCTGCCCCCGAG 
               
               
                   
                   
                 RWQEGNVFSCSVMH 
                   
                 TTCGAGGGCGGACCCAGCGTGTTCCTG 
               
               
                   
                   
                 EALHNHYTQKSLSLS 
                   
                 TTCCCCCCCAAGCCCAAGGACACCCTG 
               
               
                   
                   
                 LGKMFWVLVVVGGV 
                   
                 ATGATCAGCCGGACCCCCGAGGTGACC 
               
               
                   
                   
                 LACYSLLVTVAFIIFW 
                   
                 TGTGTGGTGGTGGACGTGTCCCAGGAG 
               
               
                   
                   
                 VRSKRSRGGHSDYM 
                   
                 GACCCCGAGGTCCAGTTCAACTGGTAC 
               
               
                   
                   
                 NMTPRRPGPTRKHYQ 
                   
                 GTGGACGGCGTGGAGGTGCACAACGC 
               
               
                   
                   
                 PYAPPRDFAAYRSRV 
                   
                 CAAGACCAAGCCCCGGGAGGAGCAGT 
               
               
                   
                   
                 KFSRSADAPAYQQGQ 
                   
                 TCCAGAGCACCTACCGGGTGGTGTCCG 
               
               
                   
                   
                 NQLYNELNLGRREEY 
                   
                 TGCTGACCGTGCTGCACCAGGACTGGC 
               
               
                   
                   
                 DVLDKRRGRDPEMG 
                   
                 TGAACGGCAAGGAATACAAGTGTAAG 
               
               
                   
                   
                 GKPRRKNPQEGLYNE 
                   
                 GTGTCCAACAAGGGCCTGCCCAGCAGC 
               
               
                   
                   
                 LQKDKMAEAYSEIG 
                   
                 ATCGAGAAAACCATCAGCAAGGCCAA 
               
               
                   
                   
                 MKGERRRGKGHDGL 
                   
                 GGGCCAGCCTCGGGAGCCCCAGGTGTA 
               
               
                   
                   
                 YQGLSTATKDTYDAL 
                   
                 CACCCTGCCCCCTAGCCAAGAGGAGAT 
               
               
                   
                   
                 HMQALPPR 
                   
                 GACCAAGAATCAGGTGTCCCTGACCTG 
               
               
                   
                   
                   
                   
                 CCTGGTGAAGGGCTTCTACCCCAGCGA 
               
               
                   
                   
                   
                   
                 CATCGCCGTGGAGTGGGAGAGCAACG 
               
               
                   
                   
                   
                   
                 GCCAGCCCGAGAACAACTACAAGACC 
               
               
                   
                   
                   
                   
                 ACCCCCCCTGTGCTGGACAGCGACGGC 
               
               
                   
                   
                   
                   
                 AGCTTCTTCCTGTACAGCAGGCTGACC 
               
               
                   
                   
                   
                   
                 GTGGACAAGAGCCGGTGGCAGGAGGG 
               
               
                   
                   
                   
                   
                 CAACGTCTTTAGCTGCTCCGTGATGCA 
               
               
                   
                   
                   
                   
                 CGAGGCCCTGCACAACCACTACACCCA 
               
               
                   
                   
                   
                   
                 GAAGAGCCTGTCCCTGAGCCTGGGCAA 
               
               
                   
                   
                   
                   
                 GATGTTCTGGGTGCTGGTCGTGGTGGG 
               
               
                   
                   
                   
                   
                 TGGCGTGCTGGCCTGCTACAGCCTGCT 
               
               
                   
                   
                   
                   
                 GGTGACAGTGGCCTTCATCATCTTTTG 
               
               
                   
                   
                   
                   
                 GGTGAGGAGCAAGCGGAGCAGAGGCG 
               
               
                   
                   
                   
                   
                 GCCACAGCGACTACATGAACATGACCC 
               
               
                   
                   
                   
                   
                 CCCGGAGGCCTGGCCCCACCCGGAAGC 
               
               
                   
                   
                   
                   
                 ACTACCAGCCCTACGCCCCTCCCAGGG 
               
               
                   
                   
                   
                   
                 ACTTCGCCGCCTACCGGAGCCGGGTGA 
               
               
                   
                   
                   
                   
                 AGTTCAGCCGGAGCGCCGACGCCCCTG 
               
               
                   
                   
                   
                   
                 CCTACCAGCAGGGCCAGAACCAGCTGT 
               
               
                   
                   
                   
                   
                 ACAACGAGCTGAACCTGGGCCGGAGG 
               
               
                   
                   
                   
                   
                 GAGGAGTACGACGTGCTGGACAAGCG 
               
               
                   
                   
                   
                   
                 GAGAGGCCGGGACCCTGAGATGGGCG 
               
               
                   
                   
                   
                   
                 GCAAGCCCCGGAGAAAGAACCCTCAG 
               
               
                   
                   
                   
                   
                 GAGGGCCTGTATAACGAACTGCAGAA 
               
               
                   
                   
                   
                   
                 AGACAAGATGGCCGAGGCCTACAGCG 
               
               
                   
                   
                   
                   
                 AGATCGGCATGAAGGGCGAGCGGCGG 
               
               
                   
                   
                   
                   
                 AGGGGCAAGGGCCACGACGGCCTGTA 
               
               
                   
                   
                   
                   
                 CCAGGGCCTGAGCACCGCCACCAAGG 
               
               
                   
                   
                   
                   
                 ATACCTACGACGCCCTGCACATGCAGG 
               
               
                   
                   
                   
                   
                 CCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 4 
                 DIKMTQSPSSMYASL 
                 151 
                 GACATCAAGATGACCCAGAGCCCCAGC 
               
               
                 (VL-VH).IgG4 
                   
                 GERVTITCKASPDINS 
                   
                 TCTATGTACGCCAGCCTGGGCGAGCGC 
               
               
                 Fcm-CD28m-Z 
                   
                 YLSWFQQKPGKSPKT 
                   
                 GTGACCATCACATGCAAGGCCAGCCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACAGCTACCTGTCCTGGTTC 
               
               
                   
                   
                 FSGGGSGQDYSLTINS 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 LEYEDMGIYYCLQYD 
                   
                 GACCCTGATCTACCGGGCCAACCGGCT 
               
               
                   
                   
                 EFPYTFGGGTKLEMK 
                   
                 GGTGGACGGCGTGCCAAGCAGATTTTC 
               
               
                   
                   
                 GSTSGSGKPGSGEGST 
                   
                 CGGCGGAGGCAGCGGCCAGGACTACA 
               
               
                   
                   
                 KGEVKLVESGGGLVK 
                   
                 GCCTGACCATCAACAGCCTGGAATACG 
               
               
                   
                   
                 PGGSLKLSCAASGFTF 
                   
                 AGGACATGGGCATCTACTACTGCCTGC 
               
               
                   
                   
                 SSYAMSWVRQIPEKR 
                   
                 AGTACGACGAGTTCCCCTACACCTTCG 
               
               
                   
                   
                 LEWVASISRGGTTYY 
                   
                 GAGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
                   
                 PDSVKGRFTISRDNVR 
                   
                 GGCAGCACCAGCGGCAGCGGCAAGCC 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 TGGAAGCGGCGAGGGCTCCACCAAGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 GCGAAGTGAAGCTGGTGGAAAGCGGC 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 GGAGGCCTGGTGAAACCTGGCGGCAG 
               
               
                   
                   
                 QGTSVTVSSESKYGPP 
                   
                 CCTGAAGCTGAGCTGCGCCGCCAGCGG 
               
               
                   
                   
                 CPPCPAPEFLGGPSVF 
                   
                 CTTCACCTTCAGCAGCTACGCCATGAG 
               
               
                   
                   
                 LFPPKPKDTLMISRTP 
                   
                 CTGGGTCCGACAGATCCCCGAGAAGCC 
               
               
                   
                   
                 EVTCVVVDVSQEDPE 
                   
                 GCTGGAATGGGTGGCCAGCATCAGCAC 
               
               
                   
                   
                 VQFNWYVDGVEVHN 
                   
                 GGGCGGCACCACCTACTACCCCGACAG 
               
               
                   
                   
                 AKTKPREEQFNSTYR 
                   
                 CGTGAAGGGCCGGTTCACCATCAGCCG 
               
               
                   
                   
                 VVSVLTVLHQDWLN 
                   
                 GGACAACGTGCGGAACATCCTGTACCT 
               
               
                   
                   
                 GKEYKCKVSNKGLPS 
                   
                 GCAGATGAGCAGCCTGCGGAGCGAGG 
               
               
                   
                   
                 SIEKTISKAKGQPREP 
                   
                 ACACCGCCATGTACTACTGCGGCAGAT 
               
               
                   
                   
                 QVYTLPPSQEEMTKN 
                   
                 ACGACTACGACGGCTACTACGCCATGG 
               
               
                   
                   
                 QVSLTCLVKGFYPSDI 
                   
                 ATTACTGGGGCCAGGGCACCAGCGTGA 
               
               
                   
                   
                 AVEWESNGQPENNY 
                   
                 CCGTGTCTAGCCAGGGAACCTCCGTGA 
               
               
                   
                   
                 KTTPPVLDSDGSFFLY 
                   
                 CAGTGTCCAGCGAGTCCAAATATGGTC 
               
               
                   
                   
                 SRLTVDKSRWQEGN 
                   
                 CCCCATGCCCACCATGCCCAGCACCTG 
               
               
                   
                   
                 VFSCSVMHEALHNHY 
                   
                 AGTTCCTGGGGGGACCATCAGTCTTCC 
               
               
                   
                   
                 TQKSLSLSLGKMFWV 
                   
                 TGTTCCCCCCAAAACCCAAGGACACTC 
               
               
                   
                   
                 LVVVGGVLACYSLLV 
                   
                 TCATGATCTCCCGGACCCCTGAGGTCA 
               
               
                   
                   
                 TVAFIIFWVRSKRSRG 
                   
                 CGTGCGTGGTGGTGGACGTGAGCCAGG 
               
               
                   
                   
                 GHSDYMNMTPRRPG 
                   
                 AAGACCCCGAGGTCCAGTTCAACTGGT 
               
               
                   
                   
                 PTRKHYQPYAPPRDF 
                   
                 ACGTGGATGGCGTGGAGGTGCATAATG 
               
               
                   
                   
                 AAYRSRVKFSRSADA 
                   
                 CCAAGACAAAGCCCCGGGAGGAGCAG 
               
               
                   
                   
                 PAYQQGQNQLYNEL 
                   
                 TTCAATAGCACCTACCGGGTGGTGTCC 
               
               
                   
                   
                 NLGRREEYDVLDKRR 
                   
                 GTGCTGACCGTGCTGCACCAGGACTGG 
               
               
                   
                   
                 GRDPEMGGKPRRKNP 
                   
                 CTGAACGGCAAGGAATACAAGTGTAA 
               
               
                   
                   
                 QEGLYNELQKDKMA 
                   
                 GGTGTCCAACAAGGGCCTGCCCAGCAG 
               
               
                   
                   
                 EAYSEIGMKGERRRG 
                   
                 CATCGAGAAAACCATCAGCAAGGCCA 
               
               
                   
                   
                 KGHDGLYQGLSTATK 
                   
                 AGGGCCAGCCTCGGGAGCCCCAGGTGT 
               
               
                   
                   
                 DTYDALHMQALPPR 
                   
                 ACACCCTGCCCCCTAGCCAAGAGGAGA 
               
               
                   
                   
                   
                   
                 TGACCAAGAATCAGGTGTCCCTGACCT 
               
               
                   
                   
                   
                   
                 GCCTGGTGAAGGGCTTCTACCCCAGCG 
               
               
                   
                   
                   
                   
                 ACATCGCCGTGGAGTGGGAGAGCAAC 
               
               
                   
                   
                   
                   
                 GGCCAGCCCGAGAACAACTACAAGAC 
               
               
                   
                   
                   
                   
                 CACCCCCCCTGTGCTGGACAGCGACGG 
               
               
                   
                   
                   
                   
                 CAGCTTCTTCCTGTACAGCAGGCTGAC 
               
               
                   
                   
                   
                   
                 CGTGGACAAGAGCCGGTGGCAGGAGG 
               
               
                   
                   
                   
                   
                 GCAACGTCTTTAGCTGCTCCGTGATGC 
               
               
                   
                   
                   
                   
                 ACGAGGCCCTGCACAACCACTACACCC 
               
               
                   
                   
                   
                   
                 AGAAGAGCCTGTCCCTGAGCCTGGGCA 
               
               
                   
                   
                   
                   
                 AGATGTTCTGGGTGCTGGTCGTGGTGG 
               
               
                   
                   
                   
                   
                 GTGGCGTGCTGGCCTGCTACAGCCTGC 
               
               
                   
                   
                   
                   
                 TGGTGACAGTGGCCTTCATCATCTTTTG 
               
               
                   
                   
                   
                   
                 GGTGAGGAGCAAGCGGAGCAGAGGCG 
               
               
                   
                   
                   
                   
                 GCCACAGCGACTACATGAACATGACCC 
               
               
                   
                   
                   
                   
                 CCCGGAGGCCTGGCCCCACCCGGAAGC 
               
               
                   
                   
                   
                   
                 ACTACCAGCCCTACGCCCCTCCCAGGG 
               
               
                   
                   
                   
                   
                 ACTTCGCCGCCTACCGGAGCCGGGTGA 
               
               
                   
                   
                   
                   
                 AGTTCAGCCGGAGCGCCGACGCCCCTG 
               
               
                   
                   
                   
                   
                 CCTACCAGCAGGGCCAGAACCAGCTGT 
               
               
                   
                   
                   
                   
                 ACAACGAGCTGAACCTGGGCCGGAGG 
               
               
                   
                   
                   
                   
                 GAGGAGTACGACGTGCTGGACAAGCG 
               
               
                   
                   
                   
                   
                 GAGAGGCCGGGACCCTGAGATGGGCG 
               
               
                   
                   
                   
                   
                 GCAAGCCCCGGAGAAAGAACCCTCAG 
               
               
                   
                   
                   
                   
                 GAGGGCCTGTATAACGAACTGCAGAA 
               
               
                   
                   
                   
                   
                 AGACAAGATGGCCGAGGCCTACAGCG 
               
               
                   
                   
                   
                   
                 AGATCGGCATGAAGGGCGAGCGGCGG 
               
               
                   
                   
                   
                   
                 AGGGGCAAGGGCCACGACGGCCTGTA 
               
               
                   
                   
                   
                   
                 CCAGGGCCTGAGCACCGCCACCAAGG 
               
               
                   
                   
                   
                   
                 ATACCTACGACGCCCTGCACATGCAGG 
               
               
                   
                   
                   
                   
                 CCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 5 
                 DIKMTQSPSSMYASL 
                 152 
                 GACATCAAGATGACCCAGAGCCCCAGC 
               
               
                 (VL-VH).CD8α.CD28z 
                   
                 GERVTITCKASPDINS 
                   
                 TCTATGTACGCCAGCCTGGGCGAGCGC 
               
               
                   
                   
                 YLSWFQQKPGKSPKT 
                   
                 GTGACCATCACATGCAAGGCCAGCCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACAGCTACCTGTCCTGGTTC 
               
               
                   
                   
                 FSGGGSGQDYSLTINS 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 LEYEDMGIYYCLQYD 
                   
                 GACCCTGATCTACCGGGCCAACCGGCT 
               
               
                   
                   
                 EFPYTFGGGTKLEMK 
                   
                 GGTGGACGGCGTGCCAAGCAGATTTTC 
               
               
                   
                   
                 GSTSGSGKPGSGEGST 
                   
                 CGGCGGAGGCAGCGGCCAGGACTACA 
               
               
                   
                   
                 KGEVKLVESGGGLVK 
                   
                 GCCTGACCATCAACAGCCTGGAATACG 
               
               
                   
                   
                 PGGSLKLSCAASGFTF 
                   
                 AGGACATGGGCATCTACTACTGCCTGC 
               
               
                   
                   
                 SSYAMSWVRQIPEKR 
                   
                 AGTACGACGAGTTCCCCTACACCTTCG 
               
               
                   
                   
                 LEWVASISRGGTTYY 
                   
                 GAGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
                   
                 PDSVKGRFTISRDNVR 
                   
                 GGCAGCACCTCCGGCAGCGGCAAGCCT 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GGCAGCGGCGAGGGCAGCACCAAGGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 CGAAGTGAAGCTGGTGGAAAGCGGCG 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 GAGGCCTGGTGAAACCTGGCGGCAGCC 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 TGAAGCTGAGCTGCGCCGCCAGCGGCT 
               
               
                   
                   
                 ASQPLSLRPEACRPAA 
                   
                 TCACCTTCAGCAGCTACGCCATGAGCT 
               
               
                   
                   
                 GGAVHTRGLDFACDI 
                   
                 GGGTCCGACAGATCCCCGAGAAGCGG 
               
               
                   
                   
                 YIWAPLAGTCGVLLL 
                   
                 CTGGAATGGGTGGCCAGCATCAGCAGG 
               
               
                   
                   
                 SLVITLYCNHRNRSK 
                   
                 GGCGGCACCACCTACTACCCCGACAGC 
               
               
                   
                   
                 RSRGGHSDYMNMTP 
                   
                 GTGAAGGGCCGGTTCACCATCAGCCGG 
               
               
                   
                   
                 RRPGPTRKHYQPYAP 
                   
                 GACAACGTGCGGAACATCCTGTACCTG 
               
               
                   
                   
                 PRDFAAYRSRVKFSR 
                   
                 CAGATGAGCAGCCTGCGGAGCGAGGA 
               
               
                   
                   
                 SADAPAYQQGQNQL 
                   
                 CACCGCCATGTACTACTGCGGCAGATA 
               
               
                   
                   
                 YNELNLGRREEYDVL 
                   
                 CGACTACGACGGCTACTACGCCATGGA 
               
               
                   
                   
                 DKRRGRDPEMGGKP 
                   
                 TTACTGGGGCCAGGGCACCAGCGTGAC 
               
               
                   
                   
                 RRKNPQEGLYNELQK 
                   
                 CGTGTCTAGCAAGCCCACCACCACCCC 
               
               
                   
                   
                 DKMAEAYSEIGMKG 
                   
                 TGCCCCTAGACCTCCAACCCCAGCCCC 
               
               
                   
                   
                 ERRRGKGHDGLYQG 
                   
                 TACAATCGCCAGCCAGCCCCTGAGCCT 
               
               
                   
                   
                 LSTATKDTYDALHM 
                   
                 GAGGCCCGAAGCCTGTAGACCTGCCGC 
               
               
                   
                   
                 QALPPR 
                   
                 TGGCGGAGCCGTGCACACCAGAGGCCT 
               
               
                   
                   
                   
                   
                 GGATTTCGCCTGCGACATCTACATCTG 
               
               
                   
                   
                   
                   
                 GGCCCCTCTGGCCGGCACCTGTGGCGT 
               
               
                   
                   
                   
                   
                 GCTGCTGCTGAGCCTGGTCATCACCCT 
               
               
                   
                   
                   
                   
                 GTACTGCAACCACCGGAATAGGAGCA 
               
               
                   
                   
                   
                   
                 AGCGGAGCAGAGGCGGCCACAGCGAC 
               
               
                   
                   
                   
                   
                 TACATGAACATGACCCCCCGGAGGCCT 
               
               
                   
                   
                   
                   
                 GGCCCCACCCGGAAGCACTACCAGCCC 
               
               
                   
                   
                   
                   
                 TACGCCCCTCCCAGGGACTTCGCCGCC 
               
               
                   
                   
                   
                   
                 TACCGGAGCCGGGTGAAGTTCAGCCGG 
               
               
                   
                   
                   
                   
                 AGCGCCGACGCCCCTGCCTACCAGCAG 
               
               
                   
                   
                   
                   
                 GGCCAGAACCAGCTGTACAACGAGCTG 
               
               
                   
                   
                   
                   
                 AACCTGGGCCGGAGGGAGGAGTACGA 
               
               
                   
                   
                   
                   
                 CGTGCTGGACAAGCGGAGAGGCCGGG 
               
               
                   
                   
                   
                   
                 ACCCTGAGATGGGCGGCAAGCCCCGG 
               
               
                   
                   
                   
                   
                 AGAAAGAACCCTCAGGAGGGCCTGTAT 
               
               
                   
                   
                   
                   
                 AACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGA 
               
               
                   
                   
                   
                   
                 AGGGCGAGCGGCGGAGGGGCAAGGGC 
               
               
                   
                   
                   
                   
                 CACGACGGCCTGTACCAGGGCCTGAGC 
               
               
                   
                   
                   
                   
                 ACCGCCACCAAGGATACCTACGACGCC 
               
               
                   
                   
                   
                   
                 CTGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 6 
                 DIKMTQSPSSMYASL 
                 153 
                 GACATCAAGATGACCCAGAGCCCCAGC 
               
               
                 (VL-VH).CD8α(2x).CD28z 
                   
                 GERVTITCKASPDINS 
                   
                 TCTATGTACGCCAGCCTGGGCGAGCGC 
               
               
                   
                   
                 YLSWFQQKPGKSPKT 
                   
                 GTGACCATCACATGCAAGGCCAGCCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACAGCTACCTGTCCTGGTTC 
               
               
                   
                   
                 FSGGGSGQDYSLTINS 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 LEYEDMGIYYCLQYD 
                   
                 GACCCTGATCTACCGGGCCAACCGGCT 
               
               
                   
                   
                 EFPYTFGGGTKLEMK 
                   
                 GGTGGACGGCGTGCCAAGCAGATTTTC 
               
               
                   
                   
                 GSTSGSGKPGSGEGST 
                   
                 CGGCGGAGGCAGCGGCCAGGACTACA 
               
               
                   
                   
                 KGEVKLVESGGGLVK 
                   
                 GCCTGACCATCAACAGCCTGGAATACG 
               
               
                   
                   
                 PGGSLKLSCAASGFTF 
                   
                 AGGACATGGGCATCTACTACTGCCTGC 
               
               
                   
                   
                 SSYAMSWVRQIPEKR 
                   
                 AGTACGACGAGTTCCCCTACACCTTCG 
               
               
                   
                   
                 LEWVASISRGGTTYY 
                   
                 GAGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
                   
                 PDSVKGRFTISRDNVR 
                   
                 GGCAGCACCTCCGGCAGCGGCAAGCCT 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GGCAGCGGCGAGGGCAGCACCAAGGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 CGAAGTGAAGCTGGTGGAAAGCGGCG 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 GAGGCCTGGTGAAACCTGGCGGCAGCC 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 TGAAGCTGAGCTGCGCCGCCAGCGGCT 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 TCACCTTCAGCAGCTACGCCATGAGCT 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 GGGTCCGACAGATCCCCGAGAAGCGG 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 CTGGAATGGGTGGCCAGCATCAGCAGG 
               
               
                   
                   
                 SQPLSLRPEACRPAAG 
                   
                 GGCGGCACCACCTACTACCCCGACAGC 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 GTGAAGGGCCGGTTCACCATCAGCCGG 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 GACAACGTGCGGAACATCCTGTACCTG 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 CAGATGAGCAGCCTGCGGAGCGAGGA 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 CACCGCCATGTACTACTGCGGCAGATA 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 CGACTACGACGGCTACTACGCCATGGA 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 TTACTGGGGCCAGGGCACCAGCGTGAC 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 CGTGTCTAGCAAACCTACTACAACTCC 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 TGCCCCCCGGCCTCCTACACCAGCTCC 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 TACTATCGCCTCCCAGCCACTCAGTCTC 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 AGACCCGAGGCTTCTAGGCCAGCGGCC 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 GGAGGCGCGGTCCACACCCGCGGGCTG 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 GACTTTGCATCCGATAAGCCCACCACC 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 ACCCCTGCCCCTAGACCTCCAACCCCA 
               
               
                   
                   
                 PPR 
                   
                 GCCCCTACAATCGCCAGCCAGCCCCTG 
               
               
                   
                   
                   
                   
                 AGCCTGAGGCCCGAAGCCTGTAGACCT 
               
               
                   
                   
                   
                   
                 GCCGCTGGCGGAGCCGTGCACACCAGA 
               
               
                   
                   
                   
                   
                 GGCCTGGATTTCGCCTGCGACATCTAC 
               
               
                   
                   
                   
                   
                 ATCTGGGCCCCTCTGGCCGGCACCTGT 
               
               
                   
                   
                   
                   
                 GGCGTGCTGCTGCTGAGCCTGGTCATC 
               
               
                   
                   
                   
                   
                 ACCCTGTACTGCAACCACCGGAATAGG 
               
               
                   
                   
                   
                   
                 AGCAAGCGGAGCAGAGGCGGCCACAG 
               
               
                   
                   
                   
                   
                 CGACTACATGAACATGACCCCCCGGAG 
               
               
                   
                   
                   
                   
                 GCCTGGCCCCACCCGGAAGCACTACCA 
               
               
                   
                   
                   
                   
                 GCCCTACGCCCCTCCCAGGGACTTCGC 
               
               
                   
                   
                   
                   
                 CGCCTACCGGAGCCGGGTGAAGTTCAG 
               
               
                   
                   
                   
                   
                 CCGGAGCGCCGACGCCCCTGCCTACCA 
               
               
                   
                   
                   
                   
                 GCAGGGCCAGAACCAGCTGTACAACG 
               
               
                   
                   
                   
                   
                 AGCTGAACCTGGGCCGGAGGGAGGAG 
               
               
                   
                   
                   
                   
                 TACGACGTGCTGGACAAGCGGAGAGG 
               
               
                   
                   
                   
                   
                 CCGGGACCCTGAGATGGGCGGCAAGC 
               
               
                   
                   
                   
                   
                 CCCGGAGAAAGAACCCTCAGGAGGGC 
               
               
                   
                   
                   
                   
                 CTGTATAACGAACTGCAGAAAGACAA 
               
               
                   
                   
                   
                   
                 GATGGCCGAGGCCTACAGCGAGATCG 
               
               
                   
                   
                   
                   
                 GCATGAAGGGCGAGCGGCGGAGGGGC 
               
               
                   
                   
                   
                   
                 AAGGGCCACGACGGCCTGTACCAGGG 
               
               
                   
                   
                   
                   
                 CCTGAGCACCGCCACCAAGGATACCTA 
               
               
                   
                   
                   
                   
                 CGACGCCCTGCACATGCAGGCCCTGCC 
               
               
                   
                   
                   
                   
                 CCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 7 
                 DIKMTQSPSSMYASL 
                 154 
                 GACATCAAGATGACCCAGAGCCCCAGC 
               
               
                 (VL-VH).CD8a(3x).CD28z 
                   
                 GERVTITCKASPDINS 
                   
                 TCTATGTACGCCAGCCTGGGCGAGCGC 
               
               
                   
                   
                 YLSWFQQKPGKSPKT 
                   
                 GTGACCATCACATGCAAGGCCAGCCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACAGCTACCTGTCCTGGTTC 
               
               
                   
                   
                 FSGGGSGQDYSLTINS 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 LEYEDMGIYYCLQYD 
                   
                 GACCCTGATCTACCGGGCCAACCGGCT 
               
               
                   
                   
                 EFPYTFGGGTKLEMK 
                   
                 GGTGGACGGCGTGCCAAGCAGATTTTC 
               
               
                   
                   
                 GSTSGSGKPGSGEGST 
                   
                 CGGCGGAGGCAGCGGCCAGGACTACA 
               
               
                   
                   
                 KGEVKLVESGGGLVK 
                   
                 GCCTGACCATCAACAGCCTGGAATACG 
               
               
                   
                   
                 PGGSLKLSCAASGFTF 
                   
                 AGGACATGGGCATCTACTACTGCCTGC 
               
               
                   
                   
                 SSYAMSWVRQIPEKR 
                   
                 AGTACGACGAGTTCCCCTACACCTTCG 
               
               
                   
                   
                 LEWVASISRGGTTYY 
                   
                 GAGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
                   
                 PDSVKGRFTISRDNVR 
                   
                 GGCAGCACCTCCGGCAGCGGCAAGCCT 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GGCAGCGGCGAGGGCAGCACCAAGGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 CGAAGTGAAGCTGGTGGAAAGCGGCG 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 GAGGCCTGGTGAAACCTGGCGGCAGCC 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 TGAAGCTGAGCTGCGCCGCCAGCGGCT 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 TCACCTTCAGCAGCTACGCCATGAGCT 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 GGGTCCGACAGATCCCCGAGAAGCGG 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 CTGGAATGGGTGGCCAGCATCAGCAGG 
               
               
                   
                   
                 SQPLSLRPEASRPAAG 
                   
                 GGCGGCACCACCTACTACCCCGACAGC 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 GTGAAGGGCCGGTTCACCATCAGCCGG 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 GACAACGTGCGGAACATCCTGTACCTG 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 CAGATGAGCAGCCTGCGGAGCGAGGA 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 CACCGCCATGTACTACTGCGGCAGATA 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 CGACTACGACGGCTACTACGCCATGGA 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 TTACTGGGGCCAGGGCACCAGCGTGAC 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 CGTGTCTAGCAAGCCTACCACCACCCC 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 CGCACCTCGTCCTCCAACCCCTGCACC 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 TACGATTGCCAGTCAGCCTCTTTCACTG 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 CGGCCTGAGGCCAGCAGACCAGCTGCC 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 GGCGGTGCCGTCCATACAAGAGGACTG 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 GACTTCGCGTCCGATAAACCTACTACC 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 ACTCCAGCCCCAAGGCCCCCAACCCCA 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 GCACCGACTATCGCATCACAGCCTTTG 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 TCACTGCGTCCTGAAGCCAGCCGGCCA 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 GCTGCAGGGGGGGCCGTCCACACAAG 
               
               
                   
                   
                 PPR 
                   
                 GGGACTCGACTTTGCGAGTGATAAGCC 
               
               
                   
                   
                   
                   
                 CACCACCACCCCTGCCCCTAGACCTCC 
               
               
                   
                   
                   
                   
                 AACCCCAGCCCCTACAATCGCCAGCCA 
               
               
                   
                   
                   
                   
                 GCCCCTGAGCCTGAGGCCCGAAGCCTG 
               
               
                   
                   
                   
                   
                 TAGACCTGCCGCTGGCGGAGCCGTGCA 
               
               
                   
                   
                   
                   
                 CACCAGAGGCCTGGATTTCGCCTGCGA 
               
               
                   
                   
                   
                   
                 CATCTACATCTGGGCCCCTCTGGCCGG 
               
               
                   
                   
                   
                   
                 CACCTGTGGCGTGCTGCTGCTGAGCCT 
               
               
                   
                   
                   
                   
                 GGTCATCACCCTGTACTGCAACCACCG 
               
               
                   
                   
                   
                   
                 GAATAGGAGCAAGCGGAGCAGAGGCG 
               
               
                   
                   
                   
                   
                 GCCACAGCGACTACATGAACATGACCC 
               
               
                   
                   
                   
                   
                 CCCGGAGGCCTGGCCCCACCCGGAAGC 
               
               
                   
                   
                   
                   
                 ACTACCAGCCCTACGCCCCTCCCAGGG 
               
               
                   
                   
                   
                   
                 ACTTCGCCGCCTACCGGAGCCGGGTGA 
               
               
                   
                   
                   
                   
                 AGTTCAGCCGGAGCGCCGACGCCCCTG 
               
               
                   
                   
                   
                   
                 CCTACCAGCAGGGCCAGAACCAGCTGT 
               
               
                   
                   
                   
                   
                 ACAACGAGCTGAACCTGGGCCGGAGG 
               
               
                   
                   
                   
                   
                 GAGGAGTACGACGTGCTGGACAAGCG 
               
               
                   
                   
                   
                   
                 GAGAGGCCGGGACCCTGAGATGGGCG 
               
               
                   
                   
                   
                   
                 GCAAGCCCCGGAGAAAGAACCCTCAG 
               
               
                   
                   
                   
                   
                 GAGGGCCTGTATAACGAACTGCAGAA 
               
               
                   
                   
                   
                   
                 AGACAAGATGGCCGAGGCCTACAGCG 
               
               
                   
                   
                   
                   
                 AGATCGGCATGAAGGGCGAGCGGCGG 
               
               
                   
                   
                   
                   
                 AGGGGCAAGGGCCACGACGGCCTGTA 
               
               
                   
                   
                   
                   
                 CCAGGGCCTGAGCACCGCCACCAAGG 
               
               
                   
                   
                   
                   
                 ATACCTACGACGCCCTGCACATGCAGG 
               
               
                   
                   
                   
                   
                 CCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 8 
                 DIKMTQSPSSMYASL 
                 155 
                 GACATCAAGATGACCCAGAGCCCCAGC 
               
               
                 (VL-VH).CD8a(4x).CD28z 
                   
                 GERVTITCKASPDINS 
                   
                 TCTATGTACGCCAGCCTGGGCGAGCGC 
               
               
                   
                   
                 YLSWFQQKPGKSPKT 
                   
                 GTGACCATCACATGCAAGGCCAGCCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACAGCTACCTGTCCTGGTTC 
               
               
                   
                   
                 FSGGGSGQDYSLTINS 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 LEYEDMGIYYCLQYD 
                   
                 GACCCTGATCTACCGGGCCAACCGGCT 
               
               
                   
                   
                 EFPYTFGGGTKLEMK 
                   
                 GGTGGACGGCGTGCCAAGCAGATTTTC 
               
               
                   
                   
                 GSTSGSGKPGSGEGST 
                   
                 CGGCGGAGGCAGCGGCCAGGACTACA 
               
               
                   
                   
                 KGEVKLVESGGGLVK 
                   
                 GCCTGACCATCAACAGCCTGGAATACG 
               
               
                   
                   
                 PGGSLKLSCAASGFTF 
                   
                 AGGACATGGGCATCTACTACTGCCTGC 
               
               
                   
                   
                 SSYAMSWVRQIPEKR 
                   
                 AGTACGACGAGTTCCCCTACACCTTCG 
               
               
                   
                   
                 LEWVASISRGGTTYY 
                   
                 GAGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
                   
                 PDSVKGRFTISRDNVR 
                   
                 GGCAGCACCTCCGGCAGCGGCAAGCCT 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GGCAGCGGCGAGGGCAGCACCAAGGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 CGAAGTGAAGCTGGTGGAAAGCGGCG 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 GAGGCCTGGTGAAACCTGGCGGCAGCC 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 TGAAGCTGAGCTGCGCCGCCAGCGGCT 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 TCACCTTCAGCAGCTACGCCATGAGCT 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 GGGTCCGACAGATCCCCGAGAAGCGG 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 CTGGAATGGGTGGCCAGCATCAGCAGG 
               
               
                   
                   
                 SQPLSLRPEASRPAAG 
                   
                 GGCGGCACCACCTACTACCCCGACAGC 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 GTGAAGGGCCGGTTCACCATCAGCCGG 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 GACAACGTGCGGAACATCCTGTACCTG 
               
               
                   
                   
                 QPLSLRPEASRPAAG 
                   
                 CAGATGAGCAGCCTGCGGAGCGAGGA 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 CACCGCCATGTACTACTGCGGCAGATA 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 CGACTACGACGGCTACTACGCCATGGA 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 TTACTGGGGCCAGGGCACCAGCGTGAC 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 CGTGTCTAGCAAGCCTACCACCACCCC 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 CGCACCTCGTCCTCCAACCCCTGCACC 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 TACGATTGCCAGTCAGCCTCTTTCACTG 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 CGGCCTGAGGCCAGCAGACCAGCTGCC 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 GGCGGTGCCGTCCATACAAGAGGACTG 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 GACTTCGCGTCCGATAAACCTACTACC 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 ACTCCAGCCCCAAGGCCCCCAACCCCA 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 GCACCGACTATCGCATCACAGCCTTTG 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 TCACTGCGTCCTGAAGCCAGCCGGCCA 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 GCTGCAGGGGGGGCCGTCCACACAAG 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 GGGACTCGACTTTGCGAGTGATAAACC 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 TACTACAACTCCTGCCCCCCGGCCTCCT 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 ACACCAGCTCCTACTATCGCCTCCCAG 
               
               
                   
                   
                 PPR 
                   
                 CCACTCAGTCTCAGACCCGAGGCTTCT 
               
               
                   
                   
                   
                   
                 AGGCCAGCGGCCGGAGGCGCGGTCCA 
               
               
                   
                   
                   
                   
                 CACCCGCGGGCTGGACTTTGCATCCGA 
               
               
                   
                   
                   
                   
                 TAAGCCCACCACCACCCCTGCCCCTAG 
               
               
                   
                   
                   
                   
                 ACCTCCAACCCCAGCCCCTACAATCGC 
               
               
                   
                   
                   
                   
                 CAGCCAGCCCCTGAGCCTGAGGCCCGA 
               
               
                   
                   
                   
                   
                 AGCCTGTAGACCTGCCGCTGGCGGAGC 
               
               
                   
                   
                   
                   
                 CGTGCACACCAGAGGCCTGGATTTCGC 
               
               
                   
                   
                   
                   
                 CTGCGACATCTACATCTGGGCCCCTCT 
               
               
                   
                   
                   
                   
                 GGCCGGCACCTGTGGCGTGCTGCTGCT 
               
               
                   
                   
                   
                   
                 GAGCCTGGTCATCACCCTGTACTGCAA 
               
               
                   
                   
                   
                   
                 CCACCGGAATAGGAGCAAGCGGAGCA 
               
               
                   
                   
                   
                   
                 GAGGCGGCCACAGCGACTACATGAAC 
               
               
                   
                   
                   
                   
                 ATGACCCCCCGGAGGCCTGGCCCCACC 
               
               
                   
                   
                   
                   
                 CGGAAGCACTACCAGCCCTACGCCCCT 
               
               
                   
                   
                   
                   
                 CCCAGGGACTTCGCCGCCTACCGGAGC 
               
               
                   
                   
                   
                   
                 CGGGTGAAGTTCAGCCGGAGCGCCGAC 
               
               
                   
                   
                   
                   
                 GCCCCTGCCTACCAGCAGGGCCAGAAC 
               
               
                   
                   
                   
                   
                 CAGCTGTACAACGAGCTGAACCTGGGC 
               
               
                   
                   
                   
                   
                 CGGAGGGAGGAGTACGACGTGCTGGA 
               
               
                   
                   
                   
                   
                 CAAGCGGAGAGGCCGGGACCCTGAGA 
               
               
                   
                   
                   
                   
                 TGGGCGGCAAGCCCCGGAGAAAGAAC 
               
               
                   
                   
                   
                   
                 CCTCAGGAGGGCCTGTATAACGAACTG 
               
               
                   
                   
                   
                   
                 CAGAAAGACAAGATGGCCGAGGCCTA 
               
               
                   
                   
                   
                   
                 CAGCGAGATCGGCATGAAGGGCGAGC 
               
               
                   
                   
                   
                   
                 GGCGGAGGGGCAAGGGCCACGACGGC 
               
               
                   
                   
                   
                   
                 CTGTACCAGGGCCTGAGCACCGCCACC 
               
               
                   
                   
                   
                   
                 AAGGATACCTACGACGCCCTGCACATG 
               
               
                   
                   
                   
                   
                 CAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 9 
                 DIKMTQSPSSMYASL 
                 156 
                 GACATCAAGATGACCCAGAGCCCCAGC 
               
               
                 (VL-VH).LNGFRECD.CD8TM.CD28z 
                   
                 GERVTITCKASPDINS 
                   
                 TCTATGTACGCCAGCCTGGGCGAGCGC 
               
               
                   
                   
                 YLSWFQQKPGKSPKT 
                   
                 GTGACCATCACATGCAAGGCCAGCCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACAGCTACCTGTCCTGGTTC 
               
               
                   
                   
                 FSGGGSGQDYSLTINS 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 LEYEDMGIYYCLQYD 
                   
                 GACCCTGATCTACCGGGCCAACCGGCT 
               
               
                   
                   
                 EFPYTFGGGTKLEMK 
                   
                 GGTGGACGGCGTGCCAAGCAGATTTTC 
               
               
                   
                   
                 GSTSGSGKPGSGEGST 
                   
                 CGGCGGAGGCAGCGGCCAGGACTACA 
               
               
                   
                   
                 KGEVKLVESGGGLVK 
                   
                 GCCTGACCATCAACAGCCTGGAATACG 
               
               
                   
                   
                 PGGSLKLSCAASGFTF 
                   
                 AGGACATGGGCATCTACTACTGCCTGC 
               
               
                   
                   
                 SSYAMSWVRQIPEKR 
                   
                 AGTACGACGAGTTCCCCTACACCTTCG 
               
               
                   
                   
                 LEWVASISRGGTTYY 
                   
                 GAGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
                   
                 PDSVKGRFTISRDNVR 
                   
                 GGCAGCACCTCCGGCAGCGGCAAGCCT 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GGCAGCGGCGAGGGCAGCACCAAGGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 CGAAGTGAAGCTGGTGGAAAGCGGCG 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 GAGGCCTGGTGAAACCTGGCGGCAGCC 
               
               
                   
                   
                 KEACPTGLYTHSGEC 
                   
                 TGAAGCTGAGCTGCGCCGCCAGCGGCT 
               
               
                   
                   
                 CKACNLGEGVAQPC 
                   
                 TCACCTTCAGCAGCTACGCCATGAGCT 
               
               
                   
                   
                 GANQTVCEPCLDSVT 
                   
                 GGGTCCGACAGATCCCCGAGAAGCGG 
               
               
                   
                   
                 FSDVVSATEPCKPCTE 
                   
                 CTGGAATGGGTGGCCAGCATCAGCAGG 
               
               
                   
                   
                 CVGLQSMSAPCVEAD 
                   
                 GGCGGCACCACCTACTACCCCGACAGC 
               
               
                   
                   
                 DAVCRCAYGYYQDE 
                   
                 GTGAAGGGCCGGTTCACCATCAGCCGG 
               
               
                   
                   
                 TTGRCEACRVCEAGS 
                   
                 GACAACGTGCGGAACATCCTGTACCTG 
               
               
                   
                   
                 GLVFSCQDKQNTVCE 
                   
                 CAGATGAGCAGCCTGCGGAGCGAGGA 
               
               
                   
                   
                 ECPDGTYSDEANHVD 
                   
                 CACCGCCATGTACTACTGCGGCAGATA 
               
               
                   
                   
                 PCLPCTVCEDTERQL 
                   
                 CGACTACGACGGCTACTACGCCATGGA 
               
               
                   
                   
                 RECTRWADAECEEIP 
                   
                 TTACTGGGGCCAGGGCACCAGCGTGAC 
               
               
                   
                   
                 GRWITRSTPPEGSDST 
                   
                 CGTGTCTAGCAAGGAGGCATGCCCCAC 
               
               
                   
                   
                 APSTQEPEAPPEQDLI 
                   
                 AGGCCTGTACACACACAGCGGTGAGTG 
               
               
                   
                   
                 ASTVAGVVTTVMGSS 
                   
                 CTGCAAAGCCTGCAACCTGGGCGAGGG 
               
               
                   
                   
                 QPVVTRGTTDNIYIW 
                   
                 TGTGGCCCAGCCTTGTGGAGCCAACCA 
               
               
                   
                   
                 APLAGTCGVLLLSLVI 
                   
                 GACCGTGTGTGAGCCCTGCCTGGACAG 
               
               
                   
                   
                 TLYCNHRNRSKRSRG 
                   
                 CGTGACGTTCTCCGACGTGGTGAGCGC 
               
               
                   
                   
                 GHSDYMNMTPRRPG 
                   
                 GACCGAGCCGTGCAAGCCGTGCACCGA 
               
               
                   
                   
                 PTRKHYQPYAPPRDF 
                   
                 GTGCGTGGGGCTCCAGAGCATGTCGGC 
               
               
                   
                   
                 AAYRSRVKFSRSADA 
                   
                 GCCGTGCGTGGAGGCCGACGACGCCGT 
               
               
                   
                   
                 PAYQQGQNQLYNEL 
                   
                 GTGCCGCTGCGCCTACGGCTACTACCA 
               
               
                   
                   
                 NLGRREEYDVLDKRR 
                   
                 GGATGAGACGACTGGGCGCTGCGAGG 
               
               
                   
                   
                 GRDPEMGGKPRRKNP 
                   
                 CGTGCCGCGTGTGCGAGGCGGGCTCGG 
               
               
                   
                   
                 QEGLYNELQKDKMA 
                   
                 GCCTCGTGTTCTCCTGCCAGGACAAGC 
               
               
                   
                   
                 EAYSEIGMKGERRRG 
                   
                 AGAACACCGTGTGCGAGGAGTGCCCCG 
               
               
                   
                   
                 KGHDGLYQGLSTATK 
                   
                 ACGGCACGTATTCCGACGAGGCCAACC 
               
               
                   
                   
                 DTYDALHMQALPPR 
                   
                 ACGTGGACCCGTGCCTGCCCTGCACCG 
               
               
                   
                   
                   
                   
                 TGTGCGAGGACACCGAGCGCCAGCTCC 
               
               
                   
                   
                   
                   
                 GCGAGTGCACACGCTGGGCCGACGCCG 
               
               
                   
                   
                   
                   
                 AGTGCGAGGAGATCCCTGGCCGTTGGA 
               
               
                   
                   
                   
                   
                 TTACACGGTCCACACCCCCAGAGGGCT 
               
               
                   
                   
                   
                   
                 CGGACAGCACAGCCCCCAGCACCCAG 
               
               
                   
                   
                   
                   
                 GAGCCTGAGGCACCTCCAGAACAAGA 
               
               
                   
                   
                   
                   
                 CCTCATAGCCAGCACGGTGGCAGGTGT 
               
               
                   
                   
                   
                   
                 GGTGACCACAGTGATGGGCAGCTCCCA 
               
               
                   
                   
                   
                   
                 GCCCGTGGTGACCCGAGGCACCACCGA 
               
               
                   
                   
                   
                   
                 CAACATCTACATCTGGGCCCCTCTGGC 
               
               
                   
                   
                   
                   
                 CGGCACCTGTGGCGTGCTGCTGCTGAG 
               
               
                   
                   
                   
                   
                 CCTGGTCATCACCCTGTACTGCAACCA 
               
               
                   
                   
                   
                   
                 CCGGAATAGGAGCAAGCGGAGCAGAG 
               
               
                   
                   
                   
                   
                 GCGGCCACAGCGACTACATGAACATGA 
               
               
                   
                   
                   
                   
                 CCCCCCGGAGGCCTGGCCCCACCCGGA 
               
               
                   
                   
                   
                   
                 AGCACTACCAGCCCTACGCCCCTCCCA 
               
               
                   
                   
                   
                   
                 GGGACTTCGCCGCCTACCGGAGCCGGG 
               
               
                   
                   
                   
                   
                 TGAAGTTCAGCCGGAGCGCCGACGCCC 
               
               
                   
                   
                   
                   
                 CTGCCTACCAGCAGGGCCAGAACCAGC 
               
               
                   
                   
                   
                   
                 TGTACAACGAGCTGAACCTGGGCCGGA 
               
               
                   
                   
                   
                   
                 GGGAGGAGTACGACGTGCTGGACAAG 
               
               
                   
                   
                   
                   
                 CGGAGAGGCCGGGACCCTGAGATGGG 
               
               
                   
                   
                   
                   
                 CGGCAAGCCCCGGAGAAAGAACCCTC 
               
               
                   
                   
                   
                   
                 AGGAGGGCCTGTATAACGAACTGCAG 
               
               
                   
                   
                   
                   
                 AAAGACAAGATGGCCGAGGCCTACAG 
               
               
                   
                   
                   
                   
                 CGAGATCGGCATGAAGGGCGAGCGGC 
               
               
                   
                   
                   
                   
                 GGAGGGGCAAGGGCCACGACGGCCTG 
               
               
                   
                   
                   
                   
                 TACCAGGGCCTGAGCACCGCCACCAAG 
               
               
                   
                   
                   
                   
                 GATACCTACGACGCCCTGCACATGCAG 
               
               
                   
                   
                   
                   
                 GCCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 10 
                 EVKLVESGGGLVKPG 
                 157 
                 GAAGTGAAGCTGGTGGAAAGCGGCGG 
               
               
                 (VH-VL).CD8a(3x).41BBz 
                   
                 GSLKLSCAASGFTFSS 
                   
                 AGGCCTGGTGAAACCTGGCGGCAGCCT 
               
               
                   
                   
                 YAMSWVRQIPEKRLE 
                   
                 GAAGCTGAGCTGCGCCGCCAGCGGCTT 
               
               
                   
                   
                 WVASISRGGTTYYPD 
                   
                 CACCTTCAGCAGCTACGCCATGAGCTG 
               
               
                   
                   
                 SVKGRFTISRDNVRNI 
                   
                 GGTCCGACAGATCCCCGAGAAGCGGCT 
               
               
                   
                   
                 LYLQMSSLRSEDTAM 
                   
                 GGAATGGGTGGCCAGCATCAGCAGGG 
               
               
                   
                   
                 YYCGRYDYDGYYAM 
                   
                 GCGGCACCACCTACTACCCCGACAGCG 
               
               
                   
                   
                 DYWGQGTSVTVSSGS 
                   
                 TGAAGGGCCGGTTCACCATCAGCCGGG 
               
               
                   
                   
                 TSGSGKPGSGEGSTK 
                   
                 ACAACGTGCGGAACATCCTGTACCTGC 
               
               
                   
                   
                 GDIKMTQSPSSMYAS 
                   
                 AGATGAGCAGCCTGCGGAGCGAGGAC 
               
               
                   
                   
                 LGERVTITCKASPDIN 
                   
                 ACCGCCATGTACTACTGCGGCAGATAC 
               
               
                   
                   
                 SYLSWFQQKPGKSPK 
                   
                 GACTACGACGGCTACTACGCCATGGAT 
               
               
                   
                   
                 TLIYRANRLVDGVPS 
                   
                 TACTGGGGCCAGGGCACCAGCGTGACC 
               
               
                   
                   
                 RFSGGGSGQDYSLTIN 
                   
                 GTGTCTAGCGGCAGCACCTCCGGCAGC 
               
               
                   
                   
                 SLEYEDMGIYYCLQY 
                   
                 GGCAAGCCTGGCAGCGGCGAGGGCAG 
               
               
                   
                   
                 DEFPYTFGGGTKLEM 
                   
                 CACCAAGGGCGACATCAAGATGACCC 
               
               
                   
                   
                 KKPTTTPAPRPPTPAP 
                   
                 AGAGCCCCAGCTCTATGTACGCCAGCC 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 TGGGCGAGCGCGTGACCATCACATGCA 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 AGGCCAGCCCCGACATCAACAGCTACC 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 TGTCCTGGTTCCAGCAGAAGCCCGGCA 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 AGAGCCCCAAGACCCTGATCTACCGGG 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 CCAACCGGCTGGTGGACGGCGTGCCAA 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 GCAGATTTTCCGGCGGAGGCAGCGGCC 
               
               
                   
                   
                 TIASQPLSLRPEACRP 
                   
                 AGGACTACAGCCTGACCATCAACAGCC 
               
               
                   
                   
                 AAGGAVHTRGLDFA 
                   
                 TGGAATACGAGGACATGGGCATCTACT 
               
               
                   
                   
                 CDIYIWAPLAGTCGV 
                   
                 ACTGCCTGCAGTACGACGAGTTCCCCT 
               
               
                   
                   
                 LLLSLVITLYCNHRNK 
                   
                 ACACCTTCGGAGGCGGCACCAAGCTGG 
               
               
                   
                   
                 RGRKKLLYIFKQPFM 
                   
                 AAATGAAGAAGCCTACCACCACCCCCG 
               
               
                   
                   
                 RPVQTTQEEDGCSCR 
                   
                 CACCTCGTCCTCCAACCCCTGCACCTA 
               
               
                   
                   
                 FPEEEEGGCELRVKFS 
                   
                 CGATTGCCAGTCAGCCTCTTTCACTGC 
               
               
                   
                   
                 RSADAPAYQQGQNQ 
                   
                 GGCCTGAGGCCAGCAGACCAGCTGCCG 
               
               
                   
                   
                 LYNELNLGRREEYDV 
                   
                 GCGGTGCCGTCCATACAAGAGGACTGG 
               
               
                   
                   
                 LDKRRGRDPEMGGK 
                   
                 ACTTCGCGTCCGATAAACCTACTACCA 
               
               
                   
                   
                 PRRKNPQEGLYNELQ 
                   
                 CTCCAGCCCCAAGGCCCCCAACCCCAG 
               
               
                   
                   
                 KDKMAEAYSEIGMK 
                   
                 CACCGACTATCGCATCACAGCCTTTGT 
               
               
                   
                   
                 GERRRGKGHDGLYQ 
                   
                 CACTGCGTCCTGAAGCCAGCCGGCCAG 
               
               
                   
                   
                 GLSTATKDTYDALH 
                   
                 CTGCAGGGGGGGCCGTCCACACAAGG 
               
               
                   
                   
                 MQALPPR 
                   
                 GGACTCGACTTTGCGAGTGATAAGCCC 
               
               
                   
                   
                   
                   
                 ACCACCACCCCTGCCCCTAGACCTCCA 
               
               
                   
                   
                   
                   
                 ACCCCAGCCCCTACAATCGCCAGCCAG 
               
               
                   
                   
                   
                   
                 CCCCTGAGCCTGAGGCCCGAAGCCTGT 
               
               
                   
                   
                   
                   
                 AGACCTGCCGCTGGCGGAGCCGTGCAC 
               
               
                   
                   
                   
                   
                 ACCAGAGGCCTGGATTTCGCCTGCGAC 
               
               
                   
                   
                   
                   
                 ATCTACATCTGGGCCCCTCTGGCCGGC 
               
               
                   
                   
                   
                   
                 ACCTGTGGCGTGCTGCTGCTGAGCCTG 
               
               
                   
                   
                   
                   
                 GTCATCACCCTGTACTGCAACCACCGG 
               
               
                   
                   
                   
                   
                 AATAAGAGAGGCCGGAAGAAACTGCT 
               
               
                   
                   
                   
                   
                 GTACATCTTCAAGCAGCCCTTCATGCG 
               
               
                   
                   
                   
                   
                 GCCCGTGCAGACCACCCAGGAAGAGG 
               
               
                   
                   
                   
                   
                 ACGGCTGCAGCTGCCGGTTCCCCGAGG 
               
               
                   
                   
                   
                   
                 AAGAGGAAGGCGGCTGCGAACTGCGG 
               
               
                   
                   
                   
                   
                 GTGAAGTTCAGCCGGAGCGCCGACGCC 
               
               
                   
                   
                   
                   
                 CCTGCCTACCAGCAGGGCCAGAACCAG 
               
               
                   
                   
                   
                   
                 CTGTACAACGAGCTGAACCTGGGCCGG 
               
               
                   
                   
                   
                   
                 AGGGAGGAGTACGACGTGCTGGACAA 
               
               
                   
                   
                   
                   
                 GCGGAGAGGCCGGGACCCTGAGATGG 
               
               
                   
                   
                   
                   
                 GCGGCAAGCCCCGGAGAAAGAACCCT 
               
               
                   
                   
                   
                   
                 CAGGAGGGCCTGTATAACGAACTGCAG 
               
               
                   
                   
                   
                   
                 AAAGACAAGATGGCCGAGGCCTACAG 
               
               
                   
                   
                   
                   
                 CGAGATCGGCATGAAGGGCGAGCGGC 
               
               
                   
                   
                   
                   
                 GGAGGGGCAAGGGCCACGACGGCCTG 
               
               
                   
                   
                   
                   
                 TACCAGGGCCTGAGCACCGCCACCAAG 
               
               
                   
                   
                   
                   
                 GATACCTACGACGCCCTGCACATGCAG 
               
               
                   
                   
                   
                   
                 GCCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine ROR1 
                 11 
                 EVKLVESGGGLVKPG 
                 158 
                 GAAGTGAAGCTGGTGGAAAGCGGCGG 
               
               
                 (VH-VL).IgG4 
                   
                 GSLKLSCAASGFTFSS 
                   
                 AGGCCTGGTGAAACCTGGCGGCAGCCT 
               
               
                 Fcm.CD8aTM.41BBz 
                   
                 YAMSWVRQIPEKRLE 
                   
                 GAAGCTGAGCTGCGCCGCCAGCGGCTT 
               
               
                   
                   
                 WVASISRGGTTYYPD 
                   
                 CACCTTCAGCAGCTACGCCATGAGCTG 
               
               
                   
                   
                 SVKGRFTISRDNVRNI 
                   
                 GGTCCGACAGATCCCCGAGAAGCGGCT 
               
               
                   
                   
                 LYLQMSSLRSEDTAM 
                   
                 GGAATGGGTGGCCAGCATCAGCAGGG 
               
               
                   
                   
                 YYCGRYDYDGYYAM 
                   
                 GCGGCACCACCTACTACCCCGACAGCG 
               
               
                   
                   
                 DYWGQGTSVTVSSGS 
                   
                 TGAAGGGCCGGTTCACCATCAGCCGGG 
               
               
                   
                   
                 TSGSGKPGSGEGSTK 
                   
                 ACAACGTGCGGAACATCCTGTACCTGC 
               
               
                   
                   
                 GDIKMTQSPSSMYAS 
                   
                 AGATGAGCAGCCTGCGGAGCGAGGAC 
               
               
                   
                   
                 LGERVTITCKASPDIN 
                   
                 ACCGCCATGTACTACTGCGGCAGATAC 
               
               
                   
                   
                 SYLSWFQQKPGKSPK 
                   
                 GACTACGACGGCTACTACGCCATGGAT 
               
               
                   
                   
                 TLIYRANRLVDGVPS 
                   
                 TACTGGGGCCAGGGCACCAGCGTGACC 
               
               
                   
                   
                 RFSGGGSGQDYSLTIN 
                   
                 GTGTCTAGCGGCAGCACCTCCGGCAGC 
               
               
                   
                   
                 SLEYEDMGIYYCLQY 
                   
                 GGCAAGCCTGGCAGCGGCGAGGGCAG 
               
               
                   
                   
                 DEFPYTFGGGTKLEM 
                   
                 CACCAAGGGCGACATCAAGATGACCC 
               
               
                   
                   
                 KESKYGPPCPPCPAPE 
                   
                 AGAGCCCCAGCTCTATGTACGCCAGCC 
               
               
                   
                   
                 FEGGPSVFLFPPKPKD 
                   
                 TGGGCGAGCGCGTGACCATCACATGCA 
               
               
                   
                   
                 TLMISRTPEVTCVVV 
                   
                 AGGCCAGCCCCGACATCAACAGCTACC 
               
               
                   
                   
                 DVSQEDPEVQFNWY 
                   
                 TGTCCTGGTTCCAGCAGAAGCCCGGCA 
               
               
                   
                   
                 VDGVEVHNAKTKPR 
                   
                 AGAGCCCCAAGACCCTGATCTACCGGG 
               
               
                   
                   
                 EEQFQSTYRVVSVLT 
                   
                 CCAACCGGCTGGTGGACGGCGTGCCAA 
               
               
                   
                   
                 VLHQDWLNGKEYKC 
                   
                 GCAGATTTTCCGGCGGAGGCAGCGGCC 
               
               
                   
                   
                 KVSNKGLPSSIEKTIS 
                   
                 AGGACTACAGCCTGACCATCAACAGCC 
               
               
                   
                   
                 KAKGQPREPQVYTLP 
                   
                 TGGAATACGAGGACATGGGCATCTACT 
               
               
                   
                   
                 PSQEEMTKNQVSLTC 
                   
                 ACTGCCTGCAGTACGACGAGTTCCCCT 
               
               
                   
                   
                 LVKGFYPSDIAVEWE 
                   
                 ACACCTTCGGAGGCGGCACCAAGCTGG 
               
               
                   
                   
                 SNGQPENNYKTTPPV 
                   
                 AAATGAAGGAGAGCAAGTACGGCCCT 
               
               
                   
                   
                 LDSDGSFFLYSRLTVD 
                   
                 CCCTGCCCCCCTTGCCCTGCCCCCGAGT 
               
               
                   
                   
                 KSRWQEGNVFSCSV 
                   
                 TCGAGGGCGGACCCAGCGTGTTCCTGT 
               
               
                   
                   
                 MHEALHNHYTQKSLS 
                   
                 TCCCCCCCAAGCCCAAGGACACCCTGA 
               
               
                   
                   
                 LSLGKMIYIWAPLAG 
                   
                 TGATCAGCCGGACCCCCGAGGTGACCT 
               
               
                   
                   
                 TCGVLLLSLVITLYCN 
                   
                 GTGTGGTGGTGGACGTGTCCCAGGAGG 
               
               
                   
                   
                 HRNKRGRKKLLYIFK 
                   
                 ACCCCGAGGTCCAGTTCAACTGGTACG 
               
               
                   
                   
                 QPFMRPVQTTQEEDG 
                   
                 TGGACGGCGTGGAGGTGCACAACGCC 
               
               
                   
                   
                 CSCRFPEEEEGGCELR 
                   
                 AAGACCAAGCCCCGGGAGGAGCAGTT 
               
               
                   
                   
                 VKFSRSADAPAYQQG 
                   
                 CCAGAGCACCTACCGGGTGGTGTCCGT 
               
               
                   
                   
                 QNQLYNELNLGRREE 
                   
                 GCTGACCGTGCTGCACCAGGACTGGCT 
               
               
                   
                   
                 YDVLDKRRGRDPEM 
                   
                 GAACGGCAAGGAATACAAGTGTAAGG 
               
               
                   
                   
                 GGKPRRKNPQEGLYN 
                   
                 TGTCCAACAAGGGCCTGCCCAGCAGCA 
               
               
                   
                   
                 ELQKDKMAEAYSEIG 
                   
                 TCGAGAAAACCATCAGCAAGGCCAAG 
               
               
                   
                   
                 MKGERRRGKGHDGL 
                   
                 GGCCAGCCTCGGGAGCCCCAGGTGTAC 
               
               
                   
                   
                 YQGLSTATKDTYDAL 
                   
                 ACCCTGCCCCCTAGCCAAGAGGAGATG 
               
               
                   
                   
                 HMQALPPR 
                   
                 ACCAAGAATCAGGTGTCCCTGACCTGC 
               
               
                   
                   
                   
                   
                 CTGGTGAAGGGCTTCTACCCCAGCGAC 
               
               
                   
                   
                   
                   
                 ATCGCCGTGGAGTGGGAGAGCAACGG 
               
               
                   
                   
                   
                   
                 CCAGCCCGAGAACAACTACAAGACCA 
               
               
                   
                   
                   
                   
                 CCCCCCCTGTGCTGGACAGCGACGGCA 
               
               
                   
                   
                   
                   
                 GCTTCTTCCTGTACAGCAGGCTGACCG 
               
               
                   
                   
                   
                   
                 TGGACAAGAGCCGGTGGCAGGAGGGC 
               
               
                   
                   
                   
                   
                 AACGTCTTTAGCTGCTCCGTGATGCAC 
               
               
                   
                   
                   
                   
                 GAGGCCCTGCACAACCACTACACCCAG 
               
               
                   
                   
                   
                   
                 AAGAGCCTGTCCCTGAGCCTGGGCAAG 
               
               
                   
                   
                   
                   
                 ATGATCTACATCTGGGCCCCTCTGGCC 
               
               
                   
                   
                   
                   
                 GGCACCTGTGGCGTGCTGCTGCTGAGC 
               
               
                   
                   
                   
                   
                 CTGGTCATCACCCTGTACTGCAACCAC 
               
               
                   
                   
                   
                   
                 CGGAATAAGAGAGGCCGGAAGAAACT 
               
               
                   
                   
                   
                   
                 GCTGTACATCTTCAAGCAGCCCTTCAT 
               
               
                   
                   
                   
                   
                 GCGGCCCGTGCAGACCACCCAGGAAG 
               
               
                   
                   
                   
                   
                 AGGACGGCTGCAGCTGCCGGTTCCCCG 
               
               
                   
                   
                   
                   
                 AGGAAGAGGAAGGCGGCTGCGAACTG 
               
               
                   
                   
                   
                   
                 CGGGTGAAGTTCAGCCGGAGCGCCGAC 
               
               
                   
                   
                   
                   
                 GCCCCTGCCTACCAGCAGGGCCAGAAC 
               
               
                   
                   
                   
                   
                 CAGCTGTACAACGAGCTGAACCTGGGC 
               
               
                   
                   
                   
                   
                 CGGAGGGAGGAGTACGACGTGCTGGA 
               
               
                   
                   
                   
                   
                 CAAGCGGAGAGGCCGGGACCCTGAGA 
               
               
                   
                   
                   
                   
                 TGGGCGGCAAGCCCCGGAGAAAGAAC 
               
               
                   
                   
                   
                   
                 CCTCAGGAGGGCCTGTATAACGAACTG 
               
               
                   
                   
                   
                   
                 CAGAAAGACAAGATGGCCGAGGCCTA 
               
               
                   
                   
                   
                   
                 CAGCGAGATCGGCATGAAGGGCGAGC 
               
               
                   
                   
                   
                   
                 GGCGGAGGGGCAAGGGCCACGACGGC 
               
               
                   
                   
                   
                   
                 CTGTACCAGGGCCTGAGCACCGCCACC 
               
               
                   
                   
                   
                   
                 AAGGATACCTACGACGCCCTGCACATG 
               
               
                   
                   
                   
                   
                 CAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 Murine 
                 12 
                 DVQITQSPSSLYASLG 
                 159 
                 GACGTGCAGATCACCCAGAGCCCCAGC 
               
               
                 ROR1_v2 VL 
                   
                 ERVTITCKASPDINSY 
                   
                 AGCCTGTATGCCAGCCTGGGCGAGAGA 
               
               
                   
                   
                 LSWFQQKPGKSPKTLI 
                   
                 GTGACCATTACCTGCAAGGCCAGCCCC 
               
               
                   
                   
                 YRANRLVDGVPSRFS 
                   
                 GACATCAACAGCTACCTGAGCTGGTTC 
               
               
                   
                   
                 GGGSGQDYSLTINSLE 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 YEDMGIYYCLQYDEF 
                   
                 GACCCTGATCTACCGGGCCAACAGACT 
               
               
                   
                   
                 PYTFGGGTKLEMK 
                   
                 GGTGGATGGCGTGCCCAGCAGATTCAG 
               
               
                   
                   
                   
                   
                 CGGCGGAGGCTCTGGCCAGGACTACAG 
               
               
                   
                   
                   
                   
                 CCTGACCATCAACTCCCTGGAATACGA 
               
               
                   
                   
                   
                   
                 GGACATGGGCATCTACTACTGCCTGCA 
               
               
                   
                   
                   
                   
                 GTACGACGAGTTCCCCTACACCTTCGG 
               
               
                   
                   
                   
                   
                 AGGCGGCACCAAGCTGGAAATGAAG 
               
               
                   
               
               
                 Murine 
                 13 
                 EVKLVESGGGLVKPG 
                 160 
                 GAAGTGAAGCTGGTGGAATCTGGCGGC 
               
               
                 RORl_v2 VH 
                   
                 GSLKLSCAASGFTFSS 
                   
                 GGACTCGTGAAGCCTGGCGGCTCTCTG 
               
               
                   
                   
                 YAMSWVRQIPEKRLE 
                   
                 AAGCTGTCTTGTGCCGCCAGCGGCTTC 
               
               
                   
                   
                 WVASISRGGTTYYPD 
                   
                 ACCTTCAGCAGCTACGCCATGAGCTGG 
               
               
                   
                   
                 SVKGRFTISRDNVRNI 
                   
                 GTGCGGCAGATCCCCGAGAAGCGGCTG 
               
               
                   
                   
                 LYLQMSSLRSEDTAM 
                   
                 GAATGGGTGGCCAGCATCAGCAGAGG 
               
               
                   
                   
                 YYCGRYDYDGYYAM 
                   
                 CGGAACCACCTACTACCCCGACTCTGT 
               
               
                   
                   
                 DYWGQGTSVTVSS 
                   
                 GAAGGGCCGGTTCACCATCAGCCGGGA 
               
               
                   
                   
                   
                   
                 CAACGTGCGGAACATCCTGTACCTGCA 
               
               
                   
                   
                   
                   
                 GATGAGCAGCCTGCGGAGCGAGGACA 
               
               
                   
                   
                   
                   
                 CCGCCATGTACTACTGTGGCAGATACG 
               
               
                   
                   
                   
                   
                 ACTACGACGGCTACTATGCCATGGATT 
               
               
                   
                   
                   
                   
                 ACTGGGGCCAGGGCACCAGCGTGACC 
               
               
                   
                   
                   
                   
                 GTGTCATCT 
               
               
                   
               
               
                 Murine 
                 14 
                 DVQITQSPSSLYASLG 
                 161 
                 GACGTGCAGATCACCCAGAGCCCCAGC 
               
               
                 ROR1_v2 
                   
                 ERVTITCKASPDINSY 
                   
                 AGCCTGTATGCCAGCCTGGGCGAGAGA 
               
               
                 (VL-VH).CD8a(3x).CD28z 
                   
                 LSWFQQKPGKSPKTLI 
                   
                 GTGACCATTACCTGCAAGGCCAGCCCC 
               
               
                   
                   
                 YRANRLVDGVPSRFS 
                   
                 GACATCAACAGCTACCTGAGCTGGTTC 
               
               
                   
                   
                 GGGSGQDYSLTINSLE 
                   
                 CAGCAGAAGCCCGGCAAGAGCCCCAA 
               
               
                   
                   
                 YEDMGIYYCLQYDEF 
                   
                 GACCCTGATCTACCGGGCCAACAGACT 
               
               
                   
                   
                 PYTFGGGTKLEMKGS 
                   
                 GGTGGATGGCGTGCCCAGCAGATTCAG 
               
               
                   
                   
                 TSGSGKPGSGEGSTK 
                   
                 CGGCGGAGGCTCTGGCCAGGACTACAG 
               
               
                   
                   
                 GEVKLVESGGGLVKP 
                   
                 CCTGACCATCAACTCCCTGGAATACGA 
               
               
                   
                   
                 GGSLKLSCAASGFTFS 
                   
                 GGACATGGGCATCTACTACTGCCTGCA 
               
               
                   
                   
                 SYAMSWVRQIPEKRL 
                   
                 GTACGACGAGTTCCCCTACACCTTCGG 
               
               
                   
                   
                 EWVASISRGGTTYYP 
                   
                 AGGCGGCACCAAGCTGGAAATGAAGG 
               
               
                   
                   
                 DSVKGRFTISRDNVR 
                   
                 GCAGCACAAGCGGCAGCGGCAAGCCT 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GGATCTGGCGAGGGAAGCACCAAGGG 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 CGAAGTGAAGCTGGTGGAATCTGGCGG 
               
               
                   
                   
                 MDYWGQGTSVTVSS 
                   
                 CGGACTCGTGAAGCCTGGCGGCTCTCT 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 GAAGCTGTCTTGTGCCGCCAGCGGCTT 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 CACCTTCAGCAGCTACGCCATGAGCTG 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 GGTGCGGCAGATCCCCGAGAAGCGGCT 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 GGAATGGGTGGCCAGCATCAGCAGAG 
               
               
                   
                   
                 SQPLSLRPEASRPAAG 
                   
                 GCGGAACCACCTACTACCCCGACTCTG 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 TGAAGGGCCGGTTCACCATCAGCCGGG 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 ACAACGTGCGGAACATCCTGTACCTGC 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 AGATGAGCAGCCTGCGGAGCGAGGAC 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 ACCGCCATGTACTACTGTGGCAGATAC 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 GACTACGACGGCTACTATGCCATGGAT 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 TACTGGGGCCAGGGCACCAGCGTGACC 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 GTGTCATCTAAGCCTACCACCACCCCC 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 GCACCTCGTCCTCCAACCCCTGCACCT 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 ACGATTGCCAGTCAGCCTCTTTCACTG 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 CGGCCTGAGGCCAGCAGACCAGCTGCC 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 GGCGGTGCCGTCCATACAAGAGGACTG 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 GACTTCGCGTCCGATAAACCTACTACC 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 ACTCCAGCCCCAAGGCCCCCAACCCCA 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 GCACCGACTATCGCATCACAGCCTTTG 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 TCACTGCGTCCTGAAGCCAGCCGGCCA 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 GCTGCAGGGGGGGCCGTCCACACAAG 
               
               
                   
                   
                 PPR 
                   
                 GGGACTCGACTTTGCGAGTGATAAGCC 
               
               
                   
                   
                   
                   
                 CACCACCACCCCTGCCCCTAGACCTCC 
               
               
                   
                   
                   
                   
                 AACCCCAGCCCCTACAATCGCCAGCCA 
               
               
                   
                   
                   
                   
                 GCCCCTGAGCCTGAGGCCCGAAGCCTG 
               
               
                   
                   
                   
                   
                 TAGACCTGCCGCTGGCGGAGCCGTGCA 
               
               
                   
                   
                   
                   
                 CACCAGAGGCCTGGATTTCGCCTGCGA 
               
               
                   
                   
                   
                   
                 CATCTACATCTGGGCCCCTCTGGCCGG 
               
               
                   
                   
                   
                   
                 CACCTGTGGCGTGCTGCTGCTGAGCCT 
               
               
                   
                   
                   
                   
                 GGTCATCACCCTGTACTGCAACCACCG 
               
               
                   
                   
                   
                   
                 GAATAGGAGCAAGCGGAGCAGAGGCG 
               
               
                   
                   
                   
                   
                 GCCACAGCGACTACATGAACATGACCC 
               
               
                   
                   
                   
                   
                 CCCGGAGGCCTGGCCCCACCCGGAAGC 
               
               
                   
                   
                   
                   
                 ACTACCAGCCCTACGCCCCTCCCAGGG 
               
               
                   
                   
                   
                   
                 ACTTCGCCGCCTACCGGAGCCGGGTGA 
               
               
                   
                   
                   
                   
                 AGTTCAGCCGGAGCGCCGACGCCCCTG 
               
               
                   
                   
                   
                   
                 CCTACCAGCAGGGCCAGAACCAGCTGT 
               
               
                   
                   
                   
                   
                 ACAACGAGCTGAACCTGGGCCGGAGG 
               
               
                   
                   
                   
                   
                 GAGGAGTACGACGTGCTGGACAAGCG 
               
               
                   
                   
                   
                   
                 GAGAGGCCGGGACCCTGAGATGGGCG 
               
               
                   
                   
                   
                   
                 GCAAGCCCCGGAGAAAGAACCCTCAG 
               
               
                   
                   
                   
                   
                 GAGGGCCTGTATAACGAACTGCAGAA 
               
               
                   
                   
                   
                   
                 AGACAAGATGGCCGAGGCCTACAGCG 
               
               
                   
                   
                   
                   
                 AGATCGGCATGAAGGGCGAGCGGCGG 
               
               
                   
                   
                   
                   
                 AGGGGCAAGGGCCACGACGGCCTGTA 
               
               
                   
                   
                   
                   
                 CCAGGGCCTGAGCACCGCCACCAAGG 
               
               
                   
                   
                   
                   
                 ATACCTACGACGCCCTGCACATGCAGG 
               
               
                   
                   
                   
                   
                 CCCTGCCCCCCAGA 
               
               
                   
               
               
                 hROR1 
                 15 
                 EVQLVESGGGLVQPG 
                 162 
                 GAGGTGCAGCTCGTGGAATCCGGCGGT 
               
               
                 VH_04 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCCTGGTGCAGCCGGGCGGCAGTCTT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGACTCTCCTGTGCGGCGTCAGGCTTT 
               
               
                   
                   
                 EWVSAISRGGTTYYA 
                   
                 ACGTTCAGTTCTTATGCCATGAGCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 GTGAGGCAAGCTCCCGGTAAGGGACTG 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GAGTGGGTCTCTGCTATCAGCCGGGGA 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGTACGACCTACTACGCTGACTCCGTA 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAAGGAAGATTTACCATAAGTCGTGAC 
               
               
                   
                   
                 S 
                   
                 AATTCCAAAAACACTCTATACTTACAG 
               
               
                   
                   
                   
                   
                 ATGAACTCGCTCAGGGCCGAAGATACC 
               
               
                   
                   
                   
                   
                 GCAGTCTACTATTGTGGGAGATACGAT 
               
               
                   
                   
                   
                   
                 TACGACGGCTACTATGCTATGGATTAT 
               
               
                   
                   
                   
                   
                 TGGGGTCAGGGTACGCTCGTGACGGTG 
               
               
                   
                   
                   
                   
                 TCCTCC 
               
               
                   
               
               
                 hROR1 
                 16 
                 DIQMTQSPSSLSASVG 
                 163 
                 GATATTCAAATGACGCAAAGTCCCAGC 
               
               
                 VL_04 
                   
                 DRVTITCQASPDINSY 
                   
                 AGCCTCTCCGCCTCCGTTGGAGACAGG 
               
               
                   
                   
                 LNWYQQKPGKAPKL 
                   
                 GTGACTATTACATGCCAAGCCAGCCCC 
               
               
                   
                   
                 LIYRANNLETGVPSRF 
                   
                 GATATTAATAGCTACTTAAATTGGTAT 
               
               
                   
                   
                 SGSGSGTDFTLTISSL 
                   
                 CAGCAGAAACCTGGGAAGGCACCTAA 
               
               
                   
                   
                 QPEDIATYYCLQYDE 
                   
                 ACTTCTCATCTACCGCGCTAACAATCT 
               
               
                   
                   
                 FPYTFGQGTKLEIK 
                   
                 GGAGACCGGCGTGCCGTCTAGATTTTC 
               
               
                   
                   
                   
                   
                 CGGCTCTGGATCAGGGACCGATTTTAC 
               
               
                   
                   
                   
                   
                 TCTGACAATTAGTTCCCTGCAACCCGA 
               
               
                   
                   
                   
                   
                 AGACATCGCCACTTATTATTGCCTGCA 
               
               
                   
                   
                   
                   
                 ATATGATGAGTTTCCTTACACATTTGGT 
               
               
                   
                   
                   
                   
                 CAGGGAACTAAACTAGAGATTAAG 
               
               
                   
               
               
                 hROR1 
                 17 
                 EVQLVESGGGLVQPG 
                 164 
                 GAAGTGCAACTGGTCGAGTCTGGGGGC 
               
               
                 VH_05 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCCTTGTGCAACCTGGAGGCAGCCTT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGACTCAGTTGCGCCGCGTCTGGTTTT 
               
               
                   
                   
                 EWVSSISRGGTTYYP 
                   
                 ACCTTCTCCTCTTACGCGATGAGCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 GTTCGCCAGGCCCCCGGCAAGGGACTT 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GAGTGGGTTAGTTCGATCTCCCGCGGA 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGCACCACATATTATCCTGACTCGGTT 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAGGGACGCTTCACTATCTCTAGGGAC 
               
               
                   
                   
                 S 
                   
                 AATTCAAAGAACACACTGTATCTCCAA 
               
               
                   
                   
                   
                   
                 ATGAACTCCTTGCGGGCCGAGGACACT 
               
               
                   
                   
                   
                   
                 GCTGTGTATTATTGCGGACGATACGAC 
               
               
                   
                   
                   
                   
                 TACGATGGGTATTACGCCATGGATTAC 
               
               
                   
                   
                   
                   
                 TGGGGGCAAGGTACACTGGTCACTGTG 
               
               
                   
                   
                   
                   
                 AGTTCG 
               
               
                   
               
               
                 hROR1 
                 18 
                 DIQMTQSPSSLSASVG 
                 165 
                 GATATTCAGATGACCCAGTCACCTTCG 
               
               
                 VL_05 
                   
                 DRVTITCKASPDINSY 
                   
                 AGTCTGAGCGCATCCGTGGGCGACAGA 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTGACCATTACCTGTAAGGCCAGCCCG 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GACATTAACAGCTACCTATCGTGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAGCAAAAGCCTGGTAAGGCCCCTAAA 
               
               
                   
                   
                 PEDIATYYCLQYDEFP 
                   
                 CTCCTTATCTACAGGGCTAATAGGTTG 
               
               
                   
                   
                 YTFGQGTKLEIK 
                   
                 GTAGACGGGGTGCCTAGCCGGTTCTCT 
               
               
                   
                   
                   
                   
                 GGTTCCGGCAGCGGTACGGACTTTACT 
               
               
                   
                   
                   
                   
                 CTGACCATAAGCTCTCTGCAACCAGAA 
               
               
                   
                   
                   
                   
                 GACATCGCAACATACTACTGTTTACAA 
               
               
                   
                   
                   
                   
                 TACGACGAATTTCCTTATACCTTTGGCC 
               
               
                   
                   
                   
                   
                 AGGGGACCAAGTTAGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 19 
                 EVQLVESGGGLVQPG 
                 166 
                 GAGGTTCAGCTGGTCGAGTCCGGGGGA 
               
               
                 VH_06 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCTTAGTGCAGCCAGGAGGCAGTCTG 
               
               
                   
                   
                 YAIIWVRQAPGKGLE 
                   
                 CGGCTCTCTTGCGCTGCAAGTGGCTTC 
               
               
                   
                   
                 WVARISRGGTTRYAD 
                   
                 ACATTCAGTTCATACGCAATCATCTGG 
               
               
                   
                   
                 SVKGRFTISADTSKET 
                   
                 GTTCGACAGGCTCCTGGTAAGGGCCTC 
               
               
                   
                   
                 AYLQMNSLRAEDTA 
                   
                 GAATGGGTCGCAAGGATATCACGAGGT 
               
               
                   
                   
                 VYYCGRYDYDGYYA 
                   
                 GGAACCACTAGATACGCAGACTCTGTT 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAGGGCAGGTTCACAATTAGCGCGGAT 
               
               
                   
                   
                   
                   
                 ACCTCCAAGGAGACTGCTTATTTACAG 
               
               
                   
                   
                   
                   
                 ATGAACTCTCTGAGAGCCGAGGACACT 
               
               
                   
                   
                   
                   
                 GCTGTTTACTACTGCGGCCGATACGAT 
               
               
                   
                   
                   
                   
                 TACGACGGATATTACGCAATGGATTAC 
               
               
                   
                   
                   
                   
                 TGGGGCCAGGGCACGCTGGTGACAGTT 
               
               
                   
                   
                   
                   
                 TCATCG 
               
               
                   
               
               
                 hROR1 
                 20 
                 DIQMTQSPSSLSASVG 
                 167 
                 GATATCCAGATGACTCAGAGTCCCAGT 
               
               
                 VL_06 
                   
                 DRVTITCKASPDINSY 
                   
                 AGCCTGTCGGCAAGCGTCGGAGATCGG 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTCACAATTACCTGCAAAGCTAGTCCT 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GATATTAATTCTTACTTGTCCTGGTATC 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 AGCAGAAGCCTGGTAAGGCCCCTAAGT 
               
               
                   
                   
                 PEDIATYYCLQYDEFP 
                   
                 TGCTCATCTATCGGGCTAACCGGCTGG 
               
               
                   
                   
                 YTFGQGTKLEIK 
                   
                 TGGACGGTGTTCCCTCTAGATTCTCAG 
               
               
                   
                   
                   
                   
                 GGAGTGGAAGCGGCACTGACTTCACCC 
               
               
                   
                   
                   
                   
                 TGACTATATCGAGCCTTCAGCCAGAGG 
               
               
                   
                   
                   
                   
                 ACATTGCCACATACTACTGTCTGCAAT 
               
               
                   
                   
                   
                   
                 ATGATGAATTTCCATATACATTCGGAC 
               
               
                   
                   
                   
                   
                 AAGGTACAAAGTTAGAAATTAAG 
               
               
                   
               
               
                 hROR1 
                 21 
                 EVQLVESGGGLVQPG 
                 168 
                 GAAGTCCAACTGGTGGAGTCTGGCGGG 
               
               
                 VH_07 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCTTGGTGCAGCCCGGTGGCTCCCTT 
               
               
                   
                   
                 YAIIWVRQAPGKGLE 
                   
                 AGGCTGTCTTGCGCTGCCAGCGGGTTC 
               
               
                   
                   
                 WVARISRGGTTRYAD 
                   
                 ACATTCAGCTCCTATGCGATTATATGG 
               
               
                   
                   
                 SVKGRFTISADTSKET 
                   
                 GTCCGACAGGCACCCGGCAAGGGATTG 
               
               
                   
                   
                 AYLQMNSLRAEDTA 
                   
                 GAGTGGGTGGCTCGCATCAGCAGAGGC 
               
               
                   
                   
                 VYYCGRYDYDGYYA 
                   
                 GGCACTACTCGTTACGCCGACTCCGTG 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAAGGCAGATTCACCATCAGTGCAGAC 
               
               
                   
                   
                   
                   
                 VACATCCAAGGAAACCGCATATCTTCAG 
               
               
                   
                   
                   
                   
                 ATGAATAGCCTGCGAGCGGAGGATACC 
               
               
                   
                   
                   
                   
                 GCCGTCTATTATTGCGGACGCTATGAT 
               
               
                   
                   
                   
                   
                 TACGACGGTTATTATGCTATGGACTAC 
               
               
                   
                   
                   
                   
                 TGGGGCCAGGGCACACTTGTGACCGTC 
               
               
                   
                   
                   
                   
                 AGTAGC 
               
               
                   
               
               
                 hROR1 
                 22 
                 DIQMTQSPSSLSASVG 
                 169 
                 GACATTCAAATGACGCAAAGCCCTAGT 
               
               
                 VL_07 
                   
                 DRVTITCRASPDINSY 
                   
                 AGCTTGTCAGCTTCTGTGGGGGACCGT 
               
               
                   
                   
                 VAWYQQKPGKAPKL 
                   
                 GTCACAATCACTTGTCGGGCCTCTCCA 
               
               
                   
                   
                 LIYRANFLESGVPSRF 
                   
                 GATATAAACTCCTACGTTGCTTGGTAT 
               
               
                   
                   
                 SGSRSGTDFTLTISSL 
                   
                 CAGCAGAAGCCCGGAAAGGCTCCGAA 
               
               
                   
                   
                 QPEDFATYYCLQYDE 
                   
                 ATTGTTGATTTATCGCGCTAATTTCTTA 
               
               
                   
                   
                 FPYTFGQGTKVEIK 
                   
                 GAGTCAGGAGTGCCCAGCCGGTTCTCA 
               
               
                   
                   
                   
                   
                 GGGTCTCGCTCTGGAACCGACTTCACA 
               
               
                   
                   
                   
                   
                 CTCACTATTTCTAGCCTACAGCCTGAG 
               
               
                   
                   
                   
                   
                 GATTTTGCAACTTACTACTGTCTACAGT 
               
               
                   
                   
                   
                   
                 ACGACGAGTTTCCGTACACTTTCGGAC 
               
               
                   
                   
                   
                   
                 AGGGGACCAAGGTGGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 23 
                 QVQLVQSGGGLVKP 
                 170 
                 CAAGTACAGCTCGTGCAGAGCGGCGGT 
               
               
                 VH_08 
                   
                 GGSLRLSCAASGFTFS 
                   
                 GGCCTGGTGAAGCCAGGAGGTAGTCTT 
               
               
                   
                   
                 SYAMSWVRQIPGKGL 
                   
                 AGACTGAGCTGTGCGGCTTCTGGTTTC 
               
               
                   
                   
                 EWVSSISRGGTTYYP 
                   
                 ACGTTCAGCAGTTATGCTATGTCCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNVK 
                   
                 GTTAGGCAAATCCCCGGCAAAGGATTG 
               
               
                   
                   
                 NTLYLQMSSLRAEDT 
                   
                 GAGTGGGTTAGCAGTATCTCAAGGGGG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGAACCACATATTATCCTGACTCTGTC 
               
               
                   
                   
                 AMDYWGQGTMVTV 
                   
                 AAAGGACGGTTTACAATCAGCCGCGAT 
               
               
                   
                   
                 SS 
                   
                 AACGTTAAAAATACCCTCTACCTCCAG 
               
               
                   
                   
                   
                   
                 ATGTCTTCGCTCCGCGCTGAAGATACA 
               
               
                   
                   
                   
                   
                 GCGGTTTACTACTGTGGCAGATACGAC 
               
               
                   
                   
                   
                   
                 TACGACGGTTATTACGCCATGGACTAC 
               
               
                   
                   
                   
                   
                 TGGGGACAGGGAACTATGGTCACAGTT 
               
               
                   
                   
                   
                   
                 AGCTCT 
               
               
                   
               
               
                 hROR1 
                 24 
                 DIKMTQSPSSLSASVG 
                 171 
                 GACATCAAAATGACGCAGTCACCTAGT 
               
               
                 VL_08 
                   
                 DRVTITCKASPDINSY 
                   
                 AGCCTCTCCGCCTCGGTTGGCGATCGG 
               
               
                   
                   
                 LSWYQQKPGKAPKTL 
                   
                 GTAACCATTACCTGCAAAGCATCTCCA 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GACATAAATAGTTATCTTAGTTGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAACAGAAACCTGGCAAAGCTCCTAAG 
               
               
                   
                   
                 YEDMAIYYCLQYDEF 
                   
                 ACCCTCATCTACCGCGCTAACCGCCTC 
               
               
                   
                   
                 PYTFGDGTKVEIK 
                   
                 GTGGATGGTGTTCCAAGTCGGTTCTCA 
               
               
                   
                   
                   
                   
                 GGAAGCGGCAGTGGCACAGACTTTACA 
               
               
                   
                   
                   
                   
                 CTGACAATTAGTTCCCTCCAGTATGAG 
               
               
                   
                   
                   
                   
                 GATATGGCCATATATTACTGCCTTCAG 
               
               
                   
                   
                   
                   
                 TATGATGAGTTTCCATACACATTCGGA 
               
               
                   
                   
                   
                   
                 GACGGTACAAAGGTGGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 25 
                 QVSLRESGGGLVQPG 
                 172 
                 CAAGTGAGCCTCCGGGAGAGTGGGGG 
               
               
                 VH_09 
                   
                 RSLRLSCTASGFTFSS 
                   
                 CGGTCTGGTCCAACCAGGACGGTCACT 
               
               
                   
                   
                 YAMTWVRQAPGKGL 
                   
                 GCGGCTGTCATGCACTGCCAGCGGCTT 
               
               
                   
                   
                 EWVASISRGGTTHFA 
                   
                 CACATTTAGCTCTTACGCCATGACTTG 
               
               
                   
                   
                 DSVKGRFTISRDNSN 
                   
                 GGTCCGCCAAGCTCCCGGTAAGGGACT 
               
               
                   
                   
                 NTLYLQMDNVRDED 
                   
                 GGAGTGGGTGGCCAGCATTAGCAGGG 
               
               
                   
                   
                 TAIYYCGRYDYDGYY 
                   
                 GTGGTACAACCCACTTCGCGGATTCAG 
               
               
                   
                   
                 AMDYWGRGTLVTVS 
                   
                 TTAAGGGGAGATTCACTATCTCCAGGG 
               
               
                   
                   
                 S 
                   
                 ATAATTCCAACAACACGCTGTACCTTC 
               
               
                   
                   
                   
                   
                 AGATGGATAACGTGAGAGACGAGGAT 
               
               
                   
                   
                   
                   
                 ACCGCGATATACTACTGTGGCCGCTAT 
               
               
                   
                   
                   
                   
                 GACTACGATGGTTATTATGCTATGGAT 
               
               
                   
                   
                   
                   
                 TACTGGGGGCGGGGCACCCTGGTGACT 
               
               
                   
                   
                   
                   
                 GTGTCCTCG 
               
               
                   
               
               
                 hROR1 
                 26 
                 DIVMTQSPSSLSASVG 
                 173 
                 GATATCGTGATGACACAGTCACCTAGC 
               
               
                 VL_09 
                   
                 DRVTITCRASPDINSY 
                   
                 TCCCTGAGCGCAAGCGTGGGGGATAGG 
               
               
                   
                   
                 LAWYQQKPGKAPKL 
                   
                 GTTACCATAACTTGCAGGGCCAGTCCC 
               
               
                   
                   
                 LIYRANSLQSGVPSRF 
                   
                 GACATCAATAGTTATTTGGCCTGGTAT 
               
               
                   
                   
                 SGSGSGTEFTLTISSLQ 
                   
                 CAACAGAAGCCTGGGAAGGCACCTAA 
               
               
                   
                   
                 PEDFATYYCLQYDEF 
                   
                 GTTGCTTATTTATAGGGCTAACTCGTTA 
               
               
                   
                   
                 PYTFGQGTKLEMK 
                   
                 CAGAGCGGTGTGCCAAGTCGGTTCTCA 
               
               
                   
                   
                   
                   
                 GGCTCAGGGTCCGGGACCGAGTTCACC 
               
               
                   
                   
                   
                   
                 CTGACCATCAGTAGCTTGCAGCCAGAA 
               
               
                   
                   
                   
                   
                 GATTTTGCCACCTACTACTGTCTTCAAT 
               
               
                   
                   
                   
                   
                 ACGATGAGTTTCCTTACACTTTTGGAC 
               
               
                   
                   
                   
                   
                 AGGGCACCAAACTAGAGATGAAG 
               
               
                   
               
               
                 hROR1 
                 27 
                 QVQLVESGGGVVQP 
                 174 
                 CAGGTTCAACTGGTAGAATCCGGCGGA 
               
               
                 VH_10 
                   
                 GRSLRLSCAASGFTFS 
                   
                 GGTGTAGTGCAGCCTGGAAGGTCATTA 
               
               
                   
                   
                 SYAMNWVRQAPAKG 
                   
                 CGGTTAAGTTGCGCCGCCTCCGGGTTC 
               
               
                   
                   
                 LEWVAIISRGGTQYY 
                   
                 ACATTTAGCAGCTATGCTATGAACTGG 
               
               
                   
                   
                 ADSVKGRFTISRDNS 
                   
                 GTGCGCCAGGCCCCTGCGAAAGGACTC 
               
               
                   
                   
                 KNTLYLQMNGLRAE 
                   
                 GAATGGGTTGCCATCATCAGCCGAGGA 
               
               
                   
                   
                 DTAVYYCGRYDYDG 
                   
                 GGCACACAGTATTATGCCGATTCTGTG 
               
               
                   
                   
                 YYAMDYWGQGTLVT 
                   
                 AAGGGTCGTTTTACTATTTCCAGAGAC 
               
               
                   
                   
                 VSS 
                   
                 AACAGTAAAAATACGCTGTACCTGCAA 
               
               
                   
                   
                   
                   
                 ATGAACGGATTGAGGGCTGAGGATACC 
               
               
                   
                   
                   
                   
                 GCCGTGTACTACTGTGGACGCTACGAC 
               
               
                   
                   
                   
                   
                 TATGATGGGTACTACGCGATGGACTAT 
               
               
                   
                   
                   
                   
                 TGGGGGCAAGGAACCCTTGTAACCGTT 
               
               
                   
                   
                   
                   
                 AGTTCA 
               
               
                   
               
               
                 hROR1 
                 28 
                 EIVLTQSPDFQSVTPK 
                 175 
                 GAGATCGTTTTGACACAGAGCCCCGAT 
               
               
                 VL_10 
                   
                 EKVTITCRASPDINSY 
                   
                 TTCCAGAGCGTCACGCCCAAGGAGAAG 
               
               
                   
                   
                 LSWYQQKPDQSPKLL 
                   
                 GTCACCATCACCTGCCGAGCCAGCCCC 
               
               
                   
                   
                 IKRANQSFSGVPSRFS 
                   
                 GACATCAACAGTTATCTTTCATGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTINSLE 
                   
                 CAACAGAAACCTGATCAGAGCCCTAAG 
               
               
                   
                   
                 AEDAAAYYCLQYDE 
                   
                 CTGCTGATTAAGCGCGCCAACCAGAGC 
               
               
                   
                   
                 FPYTFGPGTKVDIK 
                   
                 TTCTCAGGGGTTCCTTCACGGTTTTCCG 
               
               
                   
                   
                   
                   
                 GGTCAGGCAGCGGGACTGACTTCACGT 
               
               
                   
                   
                   
                   
                 TGACCATTAACTCTTTGGAGGCTGAGG 
               
               
                   
                   
                   
                   
                 ATGCTGCTGCCTATTACTGCCTTCAGTA 
               
               
                   
                   
                   
                   
                 CGACGAGTTCCCCTATACATTTGGTCCT 
               
               
                   
                   
                   
                   
                 GGAACAAAAGTGGATATAAAG 
               
               
                   
               
               
                 hROR1 
                 29 
                 QVQLVQSGAEVKKP 
                 176 
                 CAGGTGCAGCTCGTCCAGAGCGGAGCC 
               
               
                 VH_11 
                   
                 GASVKVSCKASGFTF 
                   
                 GAAGTGAAGAAGCCGGGAGCATCAGT 
               
               
                   
                   
                 SSYAMHWVRQAPGQ 
                   
                 GAAAGTTTCCTGCAAAGCAAGTGGCTT 
               
               
                   
                   
                 GLEWMGNISRGGTTN 
                   
                 CACTTTCAGCAGTTACGCGATGCACTG 
               
               
                   
                   
                 YAEKFKNRVTMTRD 
                   
                 GGTGCGGCAGGCACCAGGTCAGGGAC 
               
               
                   
                   
                 TSISTAYMELSRLRSD 
                   
                 TGGAATGGATGGGGAACATCTCTCGCG 
               
               
                   
                   
                 DTAVYYCGRYDYDG 
                   
                 GCGGAACAACCAATTACGCAGAGAAG 
               
               
                   
                   
                 YYAMDYWGQGTLVT 
                   
                 TTTAAGAATCGCGTTACGATGACCAGA 
               
               
                   
                   
                 VSS 
                   
                 GACACTTCTATTAGTACAGCCTATATG 
               
               
                   
                   
                   
                   
                 GAGTTGTCGCGTCTGAGAAGCGACGAT 
               
               
                   
                   
                   
                   
                 ACCGCTGTCTACTATTGCGGCCGGTAC 
               
               
                   
                   
                   
                   
                 GATTATGACGGCTACTATGCAATGGAT 
               
               
                   
                   
                   
                   
                 TACTGGGGACAGGGCACACTTGTGACA 
               
               
                   
                   
                   
                   
                 GTGTCTAGT 
               
               
                   
               
               
                 hROR1 
                 30 
                 DIVMTQSPLSLPVTPG 
                 177 
                 GACATTGTGATGACTCAGTCTCCACTC 
               
               
                 VL_11 
                   
                 EPASISCRSSPDINSYL 
                   
                 AGCCTGCCTGTCACGCCCGGCGAACCC 
               
               
                   
                   
                 EWYLQKPGQSPQLLI 
                   
                 GCTTCTATCTCTTGTAGGAGTAGCCCTG 
               
               
                   
                   
                 YRANDRFSGVPDRFS 
                   
                 ATATCAACAGCTACCTCGAATGGTATC 
               
               
                   
                   
                 GSGSGTDFTLKISRVE 
                   
                 TCCAGAAACCTGGTCAGAGCCCCCAGC 
               
               
                   
                   
                 AEDVGVYYCLQYDE 
                   
                 TCTTGATCTATAGAGCAAACGACAGGT 
               
               
                   
                   
                 FPYTFGQGTKVEIK 
                   
                 TCTCTGGCGTGCCTGATAGGTTTTCCGG 
               
               
                   
                   
                   
                   
                 TAGTGGCAGCGGAACCGACTTCACACT 
               
               
                   
                   
                   
                   
                 TAAGATTTCAAGGGTCGAGGCCGAGGA 
               
               
                   
                   
                   
                   
                 CGTGGGGGTGTATTACTGCTTACAGTA 
               
               
                   
                   
                   
                   
                 CGATGAGTTTCCGTATACATTCGGGCA 
               
               
                   
                   
                   
                   
                 AGGCACAAAGGTGGAAATTAAG 
               
               
                   
               
               
                 hROR1 
                 31 
                 EVQLVESGGGLVQPG 
                 178 
                 GAAGTGCAACTGGTCGAAAGTGGAGG 
               
               
                 VH_12 
                   
                 GSLRLSCTGSGFTFSS 
                   
                 GGGACTAGTGCAGCCCGGAGGGTCACT 
               
               
                   
                   
                 YAMHWLRQVPGEGL 
                   
                 GAGGCTATCATGCACCGGCTCTGGTTT 
               
               
                   
                   
                 EWVSGISRGGTIDYA 
                   
                 TACTTTTTCCAGCTATGCCATGCACTGG 
               
               
                   
                   
                 DSVKGRFTISRDDAK 
                   
                 CTCAGACAGGTTCCGGGGGAAGGACTG 
               
               
                   
                   
                 KTLSLQMNSLRAEDT 
                   
                 GAGTGGGTTAGCGGAATCTCCAGAGGC 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGAACTATTGACTACGCAGACAGCGTG 
               
               
                   
                   
                 AMDYWGQGTMVTV 
                   
                 AAAGGTAGGTTTACCATCAGCAGGGAC 
               
               
                   
                   
                 SS 
                   
                 GATGCTAAAAAGACCCTGTCACTTCAA 
               
               
                   
                   
                   
                   
                 ATGAATAGCCTGAGAGCTGAGGATACG 
               
               
                   
                   
                   
                   
                 GCCGTGTATTACTGTGGACGCTATGAC 
               
               
                   
                   
                   
                   
                 TACGATGGATATTACGCAATGGACTAC 
               
               
                   
                   
                   
                   
                 TGGGGCCAGGGAACAATGGTGACCGTC 
               
               
                   
                   
                   
                   
                 TCAAGC 
               
               
                   
               
               
                 hROR1 
                 32 
                 EIVLTQSPATLSVSPG 
                 179 
                 GAGATCGTCCTGACCCAGAGCCCAGCT 
               
               
                 VL_12 
                   
                 ERATLSCRASPDINSY 
                   
                 ACTTTGTCAGTTTCGCCAGGCGAGCGG 
               
               
                   
                   
                 LAWYQQKPGQAPRL 
                   
                 GCCACACTGAGCTGTAGGGCTTCTCCT 
               
               
                   
                   
                 LFSRANNRATGIPARF 
                   
                 GATATCAATTCTTACCTGGCCTGGTATC 
               
               
                   
                   
                 TGSGSGTDFTLTISSL 
                   
                 AACAGAAACCGGGACAGGCCCCTCGC 
               
               
                   
                   
                 EPEDFAIYYCLQYDEF 
                   
                 CTGCTGTTCTCCCGCGCCAACAATAGG 
               
               
                   
                   
                 PYTFGQGTKVEIK 
                   
                 GCGACTGGCATACCAGCTCGGTTTACT 
               
               
                   
                   
                   
                   
                 GGGAGTGGGTCAGGCACTGATTTCACG 
               
               
                   
                   
                   
                   
                 CTTACAATCAGTAGCCTGGAGCCCGAA 
               
               
                   
                   
                   
                   
                 GACTTCGCCATCTACTACTGTTTACAAT 
               
               
                   
                   
                   
                   
                 ACGATGAGTTCCCCTATACCTTCGGCC 
               
               
                   
                   
                   
                   
                 AAGGGACCAAGGTGGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 33 
                 EVQLVESGGGVVQPG 
                 180 
                 GAAGTGCAGCTAGTAGAAAGTGGTGGT 
               
               
                 VH_13 
                   
                 RSLRLSCAASGFTFSS 
                   
                 GGGGTCGTGCAGCCAGGCCGCTCGCTC 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 AGGCTGTCTTGCGCTGCGAGTGGTTTC 
               
               
                   
                   
                 EWVASISRGGTQYYA 
                   
                 ACATTCTCTTCATACGCCATGAGCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 GTGAGACAGGCTCCCGGCAAGGGCCTC 
               
               
                   
                   
                 NTLYLQMNGLRAED 
                   
                 GAATGGGTCGCATCTATAAGCAGAGGC 
               
               
                   
                   
                 TAVYYCGRYDYDGY 
                   
                 GGAACCCAGTACTACGCTGACAGTGTG 
               
               
                   
                   
                 YAMDYWGQGTLVTV 
                   
                 AAGGGTCGCTTTACAATCTCACGGGAC 
               
               
                   
                   
                 SS 
                   
                 AACAGTAAAAACACCCTCTATCTACAG 
               
               
                   
                   
                   
                   
                 ATGAATGGCTTGCGAGCTGAAGACACG 
               
               
                   
                   
                   
                   
                 GCTGTGTATTATTGCGGGCGCTATGAC 
               
               
                   
                   
                   
                   
                 TATGATGGTTACTACGCTATGGATTAC 
               
               
                   
                   
                   
                   
                 TGGGGCCAGGGCACCCTGGTTACTGTT 
               
               
                   
                   
                   
                   
                 TCATCA 
               
               
                   
               
               
                 hROR1 
                 34 
                 EIVLTQSPDFQSVTPK 
                 181 
                 GAAATAGTCCTGACCCAGAGCCCAGAC 
               
               
                 VL_13 
                   
                 EKVTITCRASPDINSY 
                   
                 TTCCAGTCCGTGACCCCTAAGGAGAAG 
               
               
                   
                   
                 LPWYQQKPDQSPKLL 
                   
                 GTTACTATCACTTGCAGGGCAAGCCCT 
               
               
                   
                   
                 IKRANQSFSGVPSRFS 
                   
                 GACATAAATTCATACCTGCCATGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTINSLE 
                   
                 CAGCAGAAGCCAGACCAGTCGCCGAA 
               
               
                   
                   
                 AEDAAAYYCLQYDE 
                   
                 GCTATTAATCAAACGCGCCAACCAGTC 
               
               
                   
                   
                 FPYTFGPGTKVDIK 
                   
                 TTTTAGCGGCGTACCATCCCGATTCTCA 
               
               
                   
                   
                   
                   
                 GGTTCGGGGTCCGGGACCGATTTCACA 
               
               
                   
                   
                   
                   
                 CTCACGATAAACTCCCTTGAGGCAGAG 
               
               
                   
                   
                   
                   
                 GATGCAGCGGCTTACTACTGTTTACAG 
               
               
                   
                   
                   
                   
                 TACGACGAGTTTCCATATACGTTCGGC 
               
               
                   
                   
                   
                   
                 CCCGGCACGAAGGTAGATATCAAG 
               
               
                   
               
               
                 hROR1 
                 35 
                 EVQLVESGGGLVQPG 
                 182 
                 GAAGTGCAGCTGGTGGAGTCTGGCGGC 
               
               
                 VH_14 
                   
                 GSLRLSCATSGFTFSS 
                   
                 GGTCTGGTGCAGCCCGGCGGCTCTCTG 
               
               
                   
                   
                 YAMSWMRQAPGKGL 
                   
                 CGCCTCTCCTGTGCCACCTCTGGTTTTA 
               
               
                   
                   
                 EWVASISRGGTTYYA 
                   
                 CATTCTCCTCCTACGCTATGTCCTGGAT 
               
               
                   
                   
                 DSVKGRFTISVDKSK 
                   
                 GCGGCAAGCCCCCGGCAAGGGCCTAG 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 AGTGGGTCGCCTCAATCAGCAGGGGCG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGACGACTTATTATGCCGATTCAGTTA 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AGGGGAGATTCACAATTTCCGTGGATA 
               
               
                   
                   
                 S 
                   
                 AATCCAAGAATACCTTATACCTCCAGA 
               
               
                   
                   
                   
                   
                 TGAACTCTCTGCGGGCCGAAGATACGG 
               
               
                   
                   
                   
                   
                 CCGTATATTATTGTGGGAGGTATGACT 
               
               
                   
                   
                   
                   
                 ACGACGGATATTACGCCATGGATTATT 
               
               
                   
                   
                   
                   
                 GGGGGCAGGGGACACTTGTTACAGTGA 
               
               
                   
                   
                   
                   
                 GTTCC 
               
               
                   
               
               
                 hROR1 
                 36 
                 DIQMTQSPSSLSASVG 
                 183 
                 GATATACAGATGACACAGAGCCCTTCA 
               
               
                 VL_14 
                   
                 DRVTITCKASPDINSY 
                   
                 AGTTTATCTGCAAGCGTCGGCGATCGT 
               
               
                   
                   
                 LNWYQQKPGKAPKL 
                   
                 GTTACAATAACTTGCAAGGCATCTCCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAATTCCTACCTCAACTGGTAT 
               
               
                   
                   
                 FSGSGSGTDYTLTISS 
                   
                 CAGCAGAAGCCTGGGAAGGCTCCTAA 
               
               
                   
                   
                 LQPEDFATYYCLQYD 
                   
                 GCTGCTTATTTACAGAGCAAATCGCCT 
               
               
                   
                   
                 EFPYTFGAGTKVEIK 
                   
                 GGTGGACGGCGTGCCCAGTCGGTTTTC 
               
               
                   
                   
                   
                   
                 CGGGTCTGGGAGCGGAACGGATTACAC 
               
               
                   
                   
                   
                   
                 ACTGACCATCTCAAGCCTGCAACCCGA 
               
               
                   
                   
                   
                   
                 AGACTTCGCTACATATTACTGCCTTCA 
               
               
                   
                   
                   
                   
                 GTATGATGAGTTCCCATATACCTTCGG 
               
               
                   
                   
                   
                   
                 CGCTGGGACCAAGGTGGAGATAAAG 
               
               
                   
               
               
                 hROR1 
                 37 
                 EVQLVESGGGLVQPG 
                 184 
                 GAGGTCCAGCTCGTCGAATCTGGCGGA 
               
               
                 VH_14-1 
                   
                 GSLRLSCASSGFTFSS 
                   
                 GGTTTAGTGCAACCAGGCGGGTCGCTC 
               
               
                   
                   
                 YAMSWRRQAPGKGL 
                   
                 CGATTAAGTTGTGCGTCCAGTGGCTTC 
               
               
                   
                   
                 EWVAGISRGGTTSYA 
                   
                 ACCTTCTCCAGCTACGCCATGTCGTGG 
               
               
                   
                   
                 DSVKGRFTISSDDSKN 
                   
                 AGGCGACAGGCTCCTGGCAAAGGCTTG 
               
               
                   
                   
                 TLYLQMNSLRAEDTA 
                   
                 GAGTGGGTTGCTGGTATCTCCCGAGGA 
               
               
                   
                   
                 VYYCGRYDYDGYYA 
                   
                 GGCACCACTAGTTACGCTGACAGTGTA 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAAGGACGTTTCACTATTTCCTCTGAC 
               
               
                   
                   
                   
                   
                 GACAGCAAGAACACACTCTATCTGCAA 
               
               
                   
                   
                   
                   
                 ATGAATAGTCTCCGTGCTGAGGACACA 
               
               
                   
                   
                   
                   
                 GCCGTGTATTATTGCGGGCGGTATGAT 
               
               
                   
                   
                   
                   
                 TACGACGGCTACTACGCTATGGACTAC 
               
               
                   
                   
                   
                   
                 TGGGGCCAGGGAACTCTGGTCACTGTG 
               
               
                   
                   
                   
                   
                 AGCTCT 
               
               
                   
               
               
                 hROR1 
                 38 
                 DIQMTQSPSSLSASVG 
                 185 
                 GATATACAGATGACTCAAAGTCCTAGC 
               
               
                 VL_14-1 
                   
                 DRVTITCRASPDINSY 
                   
                 TCCTTGAGCGCCTCAGTGGGAGATCGG 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTCACTATAACTTGTAGAGCCTCACCA 
               
               
                   
                   
                 IYRANTLESGVPSRFS 
                   
                 GATATAAACTCCTATCTCTCTTGGTATC 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 AGCAGAAGCCCGGCAAAGCACCAAAG 
               
               
                   
                   
                 PEDFATYYCLQYDEF 
                   
                 CTCTTGATCTATAGAGCTAATACGCTA 
               
               
                   
                   
                 PYTFGQGTKIEIK 
                   
                 GAGAGCGGAGTGCCTTCACGGTTTTCT 
               
               
                   
                   
                   
                   
                 GGTTCCGGGAGCGGAACCGACTTTACC 
               
               
                   
                   
                   
                   
                 CTTACAATTTCTAGCCTCCAGCCAGAG 
               
               
                   
                   
                   
                   
                 GACTTCGCAACTTACTATTGTCTCCAGT 
               
               
                   
                   
                   
                   
                 ATGATGAATTTCCTTACACCTTCGGCC 
               
               
                   
                   
                   
                   
                 AAGGGACCAAGATCGAGATAAAG 
               
               
                   
               
               
                 hROR1 
                 39 
                 EVQLVESGGGLVQPG 
                 186 
                 GAGGTGCAGCTCGTTGAGTCCGGTGGG 
               
               
                 VH_14-2 
                   
                 GSLRLSCASSGFTFSS 
                   
                 GGGCTGGTGCAGCCTGGCGGGTCTCTC 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGCCTCTCTTGTGCCTCCTCCGGCTTTA 
               
               
                   
                   
                 EWVAGISRGGTTSYA 
                   
                 CCTTCAGCAGCTATGCTATGTCATGGG 
               
               
                   
                   
                 DSVKGRFTISADTSKN 
                   
                 TGCGGCAGGCACCAGGCAAAGGTCTG 
               
               
                   
                   
                 TLYLQMNSLRAEDTA 
                   
                 GAATGGGTCGCTGGGATCAGTAGAGGC 
               
               
                   
                   
                 VYYCGRYDYDGYYA 
                   
                 GGCACAACCTCCTATGCCGACAGCGTT 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAGGGGAGGTTCACAATCTCGGCTGAT 
               
               
                   
                   
                   
                   
                 ACAAGCAAGAACACTCTGTATCTCCAA 
               
               
                   
                   
                   
                   
                 ATGAACAGTCTCCGGGCAGAGGACACC 
               
               
                   
                   
                   
                   
                 GCGGTCTATTACTGCGGCCGGTACGAC 
               
               
                   
                   
                   
                   
                 TACGACGGGTACTACGCAATGGACTAT 
               
               
                   
                   
                   
                   
                 TGGGGACAGGGAACTCTGGTTACTGTC 
               
               
                   
                   
                   
                   
                 AGCTCT 
               
               
                   
               
               
                 hROR1 
                 40 
                 DIQMTQSPSSLSASVG 
                 187 
                 GATATCCAGATGACTCAAAGCCCATCT 
               
               
                 VL_14-2 
                   
                 DRVTITCRASPDINSY 
                   
                 TCTCTCAGCGCAAGCGTGGGTGACCGA 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTGACCATCACCTGCCGGGCGTCTCCT 
               
               
                   
                   
                 IYRANTLESGVPSRFS 
                   
                 GATATCAACTCATACCTGTCCTGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAGCAGAAGCCCGGAAAGGCCCCTAA 
               
               
                   
                   
                 PEDFATYYCLQYDEF 
                   
                 GCTGCTGATCTACCGCGCAAATACACT 
               
               
                   
                   
                 PYTFGTGTKLEIK 
                   
                 GGAGAGCGGGGTCCCAAGCAGATTCA 
               
               
                   
                   
                   
                   
                 GTGGGTCCGGCAGTGGTACGGACTTTA 
               
               
                   
                   
                   
                   
                 CTCTGACCATCAGCTCCCTGCAACCGG 
               
               
                   
                   
                   
                   
                 AGGACTTTGCTACTTATTACTGTCTCCA 
               
               
                   
                   
                   
                   
                 GTACGACGAGTTCCCATACACTTTCGG 
               
               
                   
                   
                   
                   
                 AACAGGCACTAAGCTGGAGATCAAA 
               
               
                   
               
               
                 hROR1 
                 41 
                 EVQLVESGGGLVQPG 
                 188 
                 GAGGTTCAACTTGTGGAATCCGGCGGC 
               
               
                 VH_14-3 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGGTTAGTCCAGCCCGGCGGGAGCTTG 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGGCTGTCCTGCGCCGCCTCTGGATTC 
               
               
                   
                   
                 EWVASISRGGTTYYA 
                   
                 ACTTTTAGCTCCTATGCTATGTCTTGGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 TAAGGCAGGCCCCTGGTAAAGGACTAG 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 AGTGGGTGGCCTCGATCTCCCGTGGTG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GCACTACATACTACGCCGACTCCGTTA 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAGGCCGGTTTACCATCTCCCGTGACA 
               
               
                   
                   
                 S 
                   
                 ACTCTAAAAATACTTTGTACCTGCAAA 
               
               
                   
                   
                   
                   
                 TGAACTCCCTGCGGGCAGAAGACACAG 
               
               
                   
                   
                   
                   
                 CCGTGTACTATTGCGGGCGTTACGATT 
               
               
                   
                   
                   
                   
                 ACGACGGATATTACGCAATGGACTACT 
               
               
                   
                   
                   
                   
                 GGGGCCAGGGCACACTGGTCACCGTGA 
               
               
                   
                   
                   
                   
                 GCAGC 
               
               
                   
               
               
                 hROR1 
                 42 
                 DIQMTQSPSSLSASVG 
                 189 
                 GATATACAAATGACTCAGTCCCCTAGT 
               
               
                 VL_14-3 
                   
                 DRVTITCKASPDINSY 
                   
                 AGCCTTAGTGCTAGTGTGGGAGACAGA 
               
               
                   
                   
                 LNWYQQKPGKAPKL 
                   
                 GTGACCATCACCTGCAAAGCATCTCCT 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GATATCAATTCCTACCTTAACTGGTATC 
               
               
                   
                   
                 FSGSGSGTDFTLTISSL 
                   
                 AACAGAAGCCTGGCAAAGCTCCAAAG 
               
               
                   
                   
                 QPEDIATYYCLQYDE 
                   
                 CTCCTGATTTATCGCGCGAACAGATTG 
               
               
                   
                   
                 FPYTFGGGTKVEIK 
                   
                 GTCGATGGGGTCCCTTCCAGATTCAGC 
               
               
                   
                   
                   
                   
                 GGCTCAGGGTCAGGGACCGATTTCACC 
               
               
                   
                   
                   
                   
                 CTCACAATTAGTTCACTTCAGCCCGAG 
               
               
                   
                   
                   
                   
                 GACATCGCCACGTATTATTGCCTTCAG 
               
               
                   
                   
                   
                   
                 TACGATGAGTTCCCTTACACCTTTGGC 
               
               
                   
                   
                   
                   
                 GGGGGAACTAAAGTCGAAATTAAG 
               
               
                   
               
               
                 hROR1 
                 43 
                 EVQLVESGGGLVQPG 
                 190 
                 GAAGTGCAGCTTGTGGAGTCAGGAGG 
               
               
                 VH_14-4 
                   
                 GSLRLSCAASGFTFSS 
                   
                 AGGGCTAGTTCAGCCAGGCGGCTCTCT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 GAGACTATCTTGTGCTGCCTCCGGCTTC 
               
               
                   
                   
                 EWVASISRGGTTYYP 
                   
                 ACATTTAGCTCTTATGCAATGTCCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNVR 
                   
                 GTCCGCCAGGCCCCTGGTAAAGGCCTG 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GAATGGGTTGCTTCTATCTCTAGAGGC 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 GGAACCACTTACTACCCTGATTCAGTG 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAGGGGAGATTCACAATTAGTAGGGA 
               
               
                   
                   
                   
                   
                 CAACGTGCGGAACATCCTCTACCTACA 
               
               
                   
                   
                   
                   
                 GATGTCAAGTTTACGCAGTGAGGACAC 
               
               
                   
                   
                   
                   
                 TGCGATGTATTACTGCGGTCGATACGA 
               
               
                   
                   
                   
                   
                 TTATGATGGATATTATGCAATGGATTA 
               
               
                   
                   
                   
                   
                 TTGGGGCCAGGGCACTCTGGTCACAGT 
               
               
                   
                   
                   
                   
                 ATCTTCC 
               
               
                   
               
               
                 hROR1 
                 44 
                 DIQMTQSPSSLSASVG 
                 191 
                 GACATCCAGATGACCCAATCACCATCG 
               
               
                 VL_14-4 
                   
                 DRVTITCKASPDINSY 
                   
                 AGTCTTAGTGCATCCGTTGGGGATAGA 
               
               
                   
                   
                 LNWYQQKPGKAPKL 
                   
                 GTGACAATCACTTGTAAGGCATCCCCG 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GACATCAACTCATATCTTAATTGGTAT 
               
               
                   
                   
                 FSGSGSGTDYTLTISS 
                   
                 CAGCAAAAGCCGGGCAAGGCCCCTAA 
               
               
                   
                   
                 LQPEDFATYYCLQYD 
                   
                 GCTCCTGATTTATAGGGCCAACCGCCT 
               
               
                   
                   
                 EFPYTFGAGTKVEIK 
                   
                 TGTGGATGGAGTCCCCTCCCGCTTTAG 
               
               
                   
                   
                   
                   
                 TGGAAGCGGCTCTGGCACAGACTACAC 
               
               
                   
                   
                   
                   
                 CCTGACTATCAGCTCCTTGCAGCCTGA 
               
               
                   
                   
                   
                   
                 GGATTTTGCTACCTACTACTGTCTTCAG 
               
               
                   
                   
                   
                   
                 TACGATGAATTTCCATACACTTTCGGT 
               
               
                   
                   
                   
                   
                 GCTGGGACAAAAGTGGAGATCAAA 
               
               
                   
               
               
                 hROR1 
                 45 
                 EVQLVESGGGLVQPG 
                 192 
                 GAAGTCCAGCTGGTTGAGTCTGGCGGA 
               
               
                 VH_14-5 
                   
                 GSLRLSCATSGFTFSS 
                   
                 GGCCTCGTGCAGCCCGGTGGTTCCTTG 
               
               
                   
                   
                 YAMSWMRKAPGKGL 
                   
                 CGACTGTCATGCGCTACCAGCGGGTTC 
               
               
                   
                   
                 EYVASISRGGTTYYA 
                   
                 ACATTCAGCTCTTATGCAATGTCCTGG 
               
               
                   
                   
                 DSVKGRFTISVDKSK 
                   
                 ATGCGGAAGGCACCGGGTAAGGGCCT 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GGAGTATGTGGCCTCAATCTCCCGAGG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 AGGCACCACATACTATGCCGATTCTGT 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 GAAAGGCCGATTCACCATTTCTGTGGA 
               
               
                   
                   
                 S 
                   
                 TAAGTCTAAAAACACTCTCTACCTCCA 
               
               
                   
                   
                   
                   
                 GATGAACTCCCTACGTGCCGAAGACAC 
               
               
                   
                   
                   
                   
                 AGCCGTGTATTATTGCGGGCGATACGA 
               
               
                   
                   
                   
                   
                 TTATGACGGTTATTATGCGATGGATTA 
               
               
                   
                   
                   
                   
                 CTGGGGTCAAGGCACACTGGTAACAGT 
               
               
                   
                   
                   
                   
                 GTCTTCC 
               
               
                   
               
               
                 hROR1 
                 46 
                 DIQMTQSPSSLSASVG 
                 193 
                 GATATTCAGATGACACAATCACCTAGC 
               
               
                 VL_14-5 
                   
                 DRVTITCKASPDINSY 
                   
                 TCACTGTCAGCGAGCGTCGGTGACCGG 
               
               
                   
                   
                 LNWYQQKPGKAPKL 
                   
                 GTTACTATCACATGCAAAGCCTCACCC 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GATATCAATTCATACCTTAACTGGTAT 
               
               
                   
                   
                 FSGSGSGTDYTLTISS 
                   
                 CAACAAAAACCAGGAAAGGCTCCAAA 
               
               
                   
                   
                 LQPEDFATYYCLQYD 
                   
                 GCTGCTAATTTATCGGGCCAATCGGTT 
               
               
                   
                   
                 EFPYTFGAGTKVEIK 
                   
                 GGTGGATGGCGTCCCGTCGAGGTTTAG 
               
               
                   
                   
                   
                   
                 TGGCTCCGGGAGCGGGACAGACTACAC 
               
               
                   
                   
                   
                   
                 TCTTACAATTTCTTCTCTCCAGCCAGAG 
               
               
                   
                   
                   
                   
                 GACTTCGCAACCTACTACTGCTTGCAG 
               
               
                   
                   
                   
                   
                 TACGATGAATTTCCATATACCTTCGGC 
               
               
                   
                   
                   
                   
                 GCAGGGACAAAAGTGGAAATCAAA 
               
               
                   
               
               
                 hROR1 
                 47 
                 EVQLVESGGGLVQPG 
                 194 
                 GAGGTGCAGCTTGTAGAAAGCGGGGG 
               
               
                 VH_15 
                   
                 GSLRLSCVTSGFTFSS 
                   
                 GGGCCTGGTGCAACCTGGCGGGTCCCT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 GCGGCTTAGTTGCGTTACGAGCGGATT 
               
               
                   
                   
                 EWVASISRGGTTYYS 
                   
                 TACATTTTCCAGTTATGCCATGTCTTGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 GTGAGACAAGCCCCCGGTAAGGGTCTG 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GAGTGGGTGGCAAGCATTAGCCGAGG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 CGGCACTACATACTACAGTGATAGTGT 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 GAAAGGCCGTTTCACAATCAGTAGAGA 
               
               
                   
                   
                 S 
                   
                 TAATTCTAAAAACACCCTGTACTTGCA 
               
               
                   
                   
                   
                   
                 GATGAACAGCCTGCGCGCCGAGGATAC 
               
               
                   
                   
                   
                   
                 AGCCGTGTACTACTGTGGAAGATACGA 
               
               
                   
                   
                   
                   
                 CTACGATGGATATTATGCGATGGATTA 
               
               
                   
                   
                   
                   
                 CTGGGGACAGGGAACCCTTGTCACCGT 
               
               
                   
                   
                   
                   
                 TTCCTCT 
               
               
                   
               
               
                 hROR1 
                 48 
                 DIVLTQSPATLSLSPG 
                 195 
                 GACATAGTGTTGACGCAGTCCCCTGCC 
               
               
                 VL_15 
                   
                 ERATLSCKASPDINSY 
                   
                 ACCCTGAGCCTGAGCCCCGGAGAGCGA 
               
               
                   
                   
                 MNWYQQKPGQAPRL 
                   
                 GCAACGTTAAGTTGCAAGGCCAGTCCA 
               
               
                   
                   
                 LISRANRLVDGVPAR 
                   
                 GATATTAACTCATACATGAATTGGTAT 
               
               
                   
                   
                 FSGSGSGTDFTLTISSL 
                   
                 CAACAGAAACCAGGCCAGGCTCCTAG 
               
               
                   
                   
                 EPEDFAVYYCLQYDE 
                   
                 ACTTCTCATATCTCGGGCAAATCGACT 
               
               
                   
                   
                 FPYTFGQGTKVEIK 
                   
                 GGTGGATGGAGTACCCGCAAGATTCAG 
               
               
                   
                   
                   
                   
                 CGGCAGCGGCAGCGGAACGGATTTCAC 
               
               
                   
                   
                   
                   
                 GCTCACCATCTCTTCCCTTGAGCCTGAG 
               
               
                   
                   
                   
                   
                 GACTTTGCAGTCTATTATTGCTTGCAGT 
               
               
                   
                   
                   
                   
                 ATGATGAGTTCCCCTACACATTCGGGC 
               
               
                   
                   
                   
                   
                 AAGGCACAAAAGTGGAAATTAAG 
               
               
                   
               
               
                 hROR1 
                 49 
                 EVQLVESGGGLVQPG 
                 196 
                 GAGGTGCAGCTGGTGGAGAGCGGAGG 
               
               
                 VH_16 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGGCCTTGTCCAACCAGGAGGTAGCCT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CAGGCTGTCTTGCGCTGCCTCAGGATT 
               
               
                   
                   
                 EWVASISRGGTTYYD 
                   
                 TACTTTTTCATCCTACGCAATGAGCTGG 
               
               
                   
                   
                 PKFQDRATISADNSK 
                   
                 GTGCGGCAAGCCCCAGGGAAGGGATT 
               
               
                   
                   
                 NTAYLQMNSLRAEDT 
                   
                 AGAATGGGTTGCCAGCATTTCTAGGGG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGGGACGACCTACTACGATCCGAAGTT 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 TCAGGATCGCGCCACTATCTCAGCCGA 
               
               
                   
                   
                 S 
                   
                 TAACTCCAAGAATACTGCCTACTTACA 
               
               
                   
                   
                   
                   
                 GATGAACAGCCTGCGGGCCGAAGACA 
               
               
                   
                   
                   
                   
                 CGGCCGTCTACTATTGCGGCCGATATG 
               
               
                   
                   
                   
                   
                 ATTACGACGGCTATTACGCCATGGATT 
               
               
                   
                   
                   
                   
                 ACTGGGGGCAAGGGACTCTGGTCACAG 
               
               
                   
                   
                   
                   
                 TGAGCTCT 
               
               
                   
               
               
                 hROR1 
                 50 
                 DIQMTQSPSSLSASVG 
                 197 
                 GATATTCAGATGACCCAGTCGCCCAGC 
               
               
                 VL_16 
                   
                 DRVTITCKASPDINSY 
                   
                 AGTCTCTCGGCCTCAGTGGGCGACCGG 
               
               
                   
                   
                 LNWYQQKPGKAPKV 
                   
                 GTCACTATCACTTGCAAAGCAAGTCCT 
               
               
                   
                   
                 LIYRANRLVDGVPSR 
                   
                 GATATAAACTCCTATCTTAATTGGTATC 
               
               
                   
                   
                 FSGSGSGTDYTLTISS 
                   
                 AGCAGAAGCCCGGCAAGGCACCTAAG 
               
               
                   
                   
                 LQPEDFATYYCLQYD 
                   
                 GTTCTGATATATCGCGCAAATCGGCTC 
               
               
                   
                   
                 EFPYTFGQGTKVEIK 
                   
                 GTGGATGGAGTACCCAGCCGATTTTCC 
               
               
                   
                   
                   
                   
                 GGCAGCGGCTCAGGCACTGACTACACA 
               
               
                   
                   
                   
                   
                 CTGACAATCAGCAGCTTGCAGCCTGAA 
               
               
                   
                   
                   
                   
                 GATTTCGCCACATACTATTGTCTACAGT 
               
               
                   
                   
                   
                   
                 ACGACGAGTTCCCTTATACATTCGGCC 
               
               
                   
                   
                   
                   
                 AGGGGACCAAGGTCGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 51 
                 EVQLVESGGGLVQPG 
                 198 
                 GAGGTCCAACTCGTGGAGAGCGGAGG 
               
               
                 VH_17 
                   
                 GSLRLSCTGSGFTFSS 
                   
                 GGGGCTAGTGCAACCAGGTGGCTCCCT 
               
               
                   
                   
                 YAMSWLRQVPGEGL 
                   
                 CCGCTTGTCCTGTACGGGCTCGGGGTT 
               
               
                   
                   
                 EWVSSISRGGTTDYA 
                   
                 CACATTTTCATCCTATGCCATGAGCTG 
               
               
                   
                   
                 DSVKGRFTISRDDAK 
                   
                 GCTGAGACAGGTGCCTGGCGAGGGCCT 
               
               
                   
                   
                 KTLSLQMNSLRAEDT 
                   
                 GGAATGGGTGTCTAGTATCAGCAGAGG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGGTACAACTGATTACGCAGATTCCGT 
               
               
                   
                   
                 AMDYWGQGTMVTV 
                   
                 CAAGGGACGTTTTACCATCTCAAGAGA 
               
               
                   
                   
                 SS 
                   
                 CGATGCCAAGAAGACATTATCACTCCA 
               
               
                   
                   
                   
                   
                 AATGAACTCACTGAGGGCCGAGGACA 
               
               
                   
                   
                   
                   
                 CCGCTGTGTACTATTGTGGGAGATACG 
               
               
                   
                   
                   
                   
                 ACTACGACGGATACTATGCCATGGACT 
               
               
                   
                   
                   
                   
                 ATTGGGGACAAGGCACGATGGTGACG 
               
               
                   
                   
                   
                   
                 GTATCTAGC 
               
               
                   
               
               
                 hROR1 
                 52 
                 EIVLTQSPATLSVSPG 
                 199 
                 GAGATAGTGCTAACCCAGTCTCCCGCA 
               
               
                 VL_17 
                   
                 ERATLSCKASPDINSY 
                   
                 ACCCTGTCTGTGTCCCCCGGAGAGCGC 
               
               
                   
                   
                 LAWYQQKPGQAPRL 
                   
                 GCTACTCTGAGCTGCAAAGCCAGCCCG 
               
               
                   
                   
                 LFSRANRLVDGIPARF 
                   
                 GACATTAATTCCTACCTTGCCTGGTATC 
               
               
                   
                   
                 TGSGSGTDFTLTISSL 
                   
                 AGCAGAAGCCTGGACAGGCCCCAAGA 
               
               
                   
                   
                 EPEDFAIYYCLQYDEF 
                   
                 TTGCTCTTTTCACGCGCCAACCGCCTGG 
               
               
                   
                   
                 PYTFGQGTKVEIK 
                   
                 TAGATGGTATTCCAGCTAGGTTTACGG 
               
               
                   
                   
                   
                   
                 GCTCAGGCAGCGGAACAGACTTCACTC 
               
               
                   
                   
                   
                   
                 TCACTATTAGCTCATTGGAGCCTGAGG 
               
               
                   
                   
                   
                   
                 ACTTTGCAATTTACTATTGTCTTCAGTA 
               
               
                   
                   
                   
                   
                 CGACGAGTTCCCATATACTTTCGGCCA 
               
               
                   
                   
                   
                   
                 GGGCACAAAAGTAGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 53 
                 EVQLVESGGGLVQPG 
                 200 
                 GAGGTTCAACTCGTGGAGTCTGGAGGC 
               
               
                 VH_18 
                   
                 GSLRLSCSASGFTFSS 
                   
                 GGGCTAGTGCAGCCTGGCGGCTCCCTG 
               
               
                   
                   
                 YAMSWVRQVPGKGL 
                   
                 CGACTGTCTTGCAGCGCATCAGGCTTT 
               
               
                   
                   
                 VWISSISRGGTTYYAD 
                   
                 ACATTCAGTTCTTATGCCATGAGCTGG 
               
               
                   
                   
                 SVRGRFIISRDNAKNT 
                   
                 GTGAGGCAGGTGCCCGGCAAGGGTCTG 
               
               
                   
                   
                 LYLEMNNLRGEDTA 
                   
                 GTGTGGATCAGCTCAATCTCCAGGGGC 
               
               
                   
                   
                 VYYCARYDYDGYYA 
                   
                 GGGACTACATATTACGCCGATTCGGTC 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AGGGGTCGTTTTATCATTAGCAGGGAT 
               
               
                   
                   
                   
                   
                 AATGCCAAGAACACCTTGTATTTGGAG 
               
               
                   
                   
                   
                   
                 ATGAACAACCTAAGAGGCGAAGACAC 
               
               
                   
                   
                   
                   
                 CGCTGTGTACTATTGTGCCCGTTACGA 
               
               
                   
                   
                   
                   
                 CTACGATGGGTACTACGCCATGGACTA 
               
               
                   
                   
                   
                   
                 TTGGGGCCAGGGAACCTTGGTGACTGT 
               
               
                   
                   
                   
                   
                 GTCAAGT 
               
               
                   
               
               
                 hROR1 
                 54 
                 DIQLTQSPDSLAVSLG 
                 201 
                 GACATACAGTTGACTCAGTCACCGGAT 
               
               
                 VL_18 
                   
                 ERATINCKASPDINSY 
                   
                 TCGCTGGCAGTTTCGCTGGGTGAGAGA 
               
               
                   
                   
                 LSWYQQRPGQPPRLL 
                   
                 GCAACCATCAACTGCAAAGCATCTCCC 
               
               
                   
                   
                 IHRANRLVDGVPDRF 
                   
                 GATATCAACTCTTATCTGTCTTGGTATC 
               
               
                   
                   
                 SGSGFGTDFTLTITSL 
                   
                 AGCAGCGTCCGGGACAACCCCCTAGGC 
               
               
                   
                   
                 QAEDVAIYYCLQYDE 
                   
                 TGCTTATTCACCGAGCCAACAGGCTGG 
               
               
                   
                   
                 FPYTFGQGTKLEIK 
                   
                 TGGACGGGGTGCCAGACCGCTTCTCGG 
               
               
                   
                   
                   
                   
                 GATCAGGATTTGGAACCGATTTTACCC 
               
               
                   
                   
                   
                   
                 TAACAATTACTAGTCTCCAAGCGGAAG 
               
               
                   
                   
                   
                   
                 ACGTGGCGATCTATTATTGTCTACAAT 
               
               
                   
                   
                   
                   
                 ATGACGAGTTCCCCTACACCTTCGGCC 
               
               
                   
                   
                   
                   
                 AGGGCACGAAGTTGGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 55 
                 EVQLVESGGGLVQPG 
                 202 
                 GAGGTCCAGCTCGTCGAATCCGGTGGA 
               
               
                 VH_19 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGGCTAGTTCAGCCAGGCGGCTCATTG 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGTTTGTCTTGTGCCGCCTCCGGTTTCA 
               
               
                   
                   
                 EWVASISRGGTTYYA 
                   
                 CATTCTCTTCTTACGCTATGTCCTGGGT 
               
               
                   
                   
                 DSVKGRFTISADTSKN 
                   
                 CCGACAAGCCCCAGGAAAAGGCTTGG 
               
               
                   
                   
                 TAYLQMNSLRAEDTA 
                   
                 AATGGGTGGCCAGTATCAGTAGAGGTG 
               
               
                   
                   
                 VYYCARYDYDGYYA 
                   
                 GGACTACATATTATGCCGACTCCGTGA 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AGGGCAGATTCACCATCTCAGCTGACA 
               
               
                   
                   
                   
                   
                 CCAGTAAGAACACTGCCTACCTACAGA 
               
               
                   
                   
                   
                   
                 TGAACAGCCTTCGGGCCGAGGACACCG 
               
               
                   
                   
                   
                   
                 CTGTGTATTACTGTGCCCGGTACGATT 
               
               
                   
                   
                   
                   
                 ATGATGGATATTATGCTATGGACTATT 
               
               
                   
                   
                   
                   
                 GGGGTCAGGGGACCTTGGTGACCGTCT 
               
               
                   
                   
                   
                   
                 CTAGC 
               
               
                   
               
               
                 hROR1 
                 56 
                 DIQMTQSPSSLSASVG 
                 203 
                 GACATTCAGATGACTCAATCGCCGAGT 
               
               
                 VL_19 
                   
                 DRVTITCKASPDINSY 
                   
                 TCTCTTAGCGCTTCTGTTGGGGACCGG 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTGACAATCACATGCAAGGCCTCTCCC 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GATATAAACTCCTATCTAAGCTGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAGCAGAAGCCAGGGAAGGCCCCCAA 
               
               
                   
                   
                 PEDFATYYCLQYDEF 
                   
                 GTTGTTAATCTATCGCGCCAACAGACT 
               
               
                   
                   
                 PYTFGQGTKVEIK 
                   
                 GGTGGATGGGGTGCCCTCTCGATTCTC 
               
               
                   
                   
                   
                   
                 CGGGAGTGGCAGTGGGACTGATTTTAC 
               
               
                   
                   
                   
                   
                 ACTGACCATTTCCTCATTGCAGCCCGA 
               
               
                   
                   
                   
                   
                 AGACTTCGCTACCTATTACTGCTTGCA 
               
               
                   
                   
                   
                   
                 GTACGATGAGTTCCCATATACATTCGG 
               
               
                   
                   
                   
                   
                 TCAGGGGACTAAAGTGGAGATAAAA 
               
               
                   
               
               
                 hROR1 
                 57 
                 EVQLLESGGGLVQPG 
                 204 
                 GAGGTACAGCTGCTGGAATCTGGTGGG 
               
               
                 VH_20 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGGCTGGTCCAGCCAGGGGGGTCACTA 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGACTGAGCTGCGCTGCCTCCGGTTTT 
               
               
                   
                   
                 EWVSSISRGGTTYYA 
                   
                 ACATTCAGCAGCTATGCAATGTCATGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 GTCAGACAGGCACCAGGTAAAGGCCTC 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GAATGGGTATCCTCCATCTCACGTGGT 
               
               
                   
                   
                 AVYYCARYDYDGYY 
                   
                 GGGACCACTTACTATGCCGATAGTGTG 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAGGGCAGGTTCACGATCTCAAGAGAT 
               
               
                   
                   
                 S 
                   
                 AATTCAAAGAATACACTCTATCTACAA 
               
               
                   
                   
                   
                   
                 ATGAACAGTTTAAGGGCCGAGGACACC 
               
               
                   
                   
                   
                   
                 GCTGTTTACTATTGTGCCAGATATGACT 
               
               
                   
                   
                   
                   
                 ACGACGGTTATTATGCTATGGATTACT 
               
               
                   
                   
                   
                   
                 GGGGACAAGGAACGCTGGTAACTGTTA 
               
               
                   
                   
                   
                   
                 GCTCT 
               
               
                   
               
               
                 hROR1 
                 58 
                 DIQMTQSPSSLSASVG 
                 205 
                 GACATCCAAATGACCCAGTCGCCTTCC 
               
               
                 VL_20 
                   
                 DRVTITCKASPDINSY 
                   
                 TCCTTGTCTGCATCTGTCGGAGATCGG 
               
               
                   
                   
                 LSWYQQKPGEAPKLL 
                   
                 GTGACGATCACTTGCAAAGCGAGTCCA 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GACATCAACTCATATCTGTCCTGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAGCAGAAGCCGGGAGAGGCACCTAA 
               
               
                   
                   
                 PEDFATYYCLQYDEF 
                   
                 GCTCCTGATCTACAGAGCAAACAGATT 
               
               
                   
                   
                 PYTFGQGTKVEIK 
                   
                 AGTGGATGGTGTGCCCTCACGGTTTTC 
               
               
                   
                   
                   
                   
                 TGGCTCCGGGTCCGGCACCGATTTCAC 
               
               
                   
                   
                   
                   
                 CTTGACCATCTCATCCCTACAGCCCGA 
               
               
                   
                   
                   
                   
                 GGATTTCGCTACTTACTATTGCTTACAG 
               
               
                   
                   
                   
                   
                 TATGATGAGTTTCCATACACCTTCGGTC 
               
               
                   
                   
                   
                   
                 AAGGCACCAAGGTTGAGATTAAG 
               
               
                   
               
               
                 hROR1 
                 59 
                 EVQLLETGGGLVKPG 
                 206 
                 GAAGTTCAACTGCTTGAGACCGGAGGC 
               
               
                 VH_21 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCCTGGTAAAACCTGGGGGCTCACTG 
               
               
                   
                   
                 YAMSWIRQAPGKGLE 
                   
                 AGGCTGAGTTGTGCCGCTTCTGGGTTC 
               
               
                   
                   
                 WVASISRGGTTYYGD 
                   
                 ACCTTTTCATCCTATGCGATGTCATGGA 
               
               
                   
                   
                 SVKGRFTISRDHAKN 
                   
                 TACGGCAGGCTCCTGGGAAGGGGCTTG 
               
               
                   
                   
                 SLYLQMNSLRVEDTA 
                   
                 AGTGGGTTGCATCAATTTCACGAGGTG 
               
               
                   
                   
                 VYYCVRYDYDGYYA 
                   
                 GGACAACTTATTATGGGGATTCCGTTA 
               
               
                   
                   
                 MDYWGLGTLVTVSS 
                   
                 AAGGTAGATTTACGATCTCTAGAGACC 
               
               
                   
                   
                   
                   
                 ATGCCAAAAATTCTCTCTATCTCCAGA 
               
               
                   
                   
                   
                   
                 TGAATAGTCTTAGGGTGGAGGACACCG 
               
               
                   
                   
                   
                   
                 CTGTGTACTACTGTGTCCGGTACGACT 
               
               
                   
                   
                   
                   
                 ATGATGGGTACTATGCTATGGACTATT 
               
               
                   
                   
                   
                   
                 GGGGGCTCGGCACTCTGGTCACTGTTA 
               
               
                   
                   
                   
                   
                 GCTCT 
               
               
                   
               
               
                 hROR1 
                 60 
                 AIRMTQSPSFLSASVG 
                 207 
                 GCCATCCGCATGACACAATCTCCCTCC 
               
               
                 VL_21 
                   
                 DRVTITCKASPDINSY 
                   
                 TTCCTTTCTGCCAGTGTCGGGGACAGA 
               
               
                   
                   
                 LSWYQQRPGKAPKLL 
                   
                 GTGACTATCACATGCAAAGCCAGCCCA 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GATATTAATTCGTACCTGTCTTGGTATC 
               
               
                   
                   
                 GGGSGTDFTLTISSLQ 
                   
                 AGCAGAGGCCCGGCAAGGCACCAAAG 
               
               
                   
                   
                 PEDIATYYCLQYDEFP 
                   
                 CTGTTGATATATCGGGCCAACCGCTTA 
               
               
                   
                   
                 YTFGQGTKLEIK 
                   
                 GTGGACGGTGTCCCCTCTCGATTCAGC 
               
               
                   
                   
                   
                   
                 GGAGGCGGTAGCGGGACGGACTTTAC 
               
               
                   
                   
                   
                   
                 ACTGACCATCTCCAGTCTCCAACCCGA 
               
               
                   
                   
                   
                   
                 GGATATTGCCACTTACTATTGTCTTCAG 
               
               
                   
                   
                   
                   
                 TATGACGAGTTCCCCTACACATTTGGA 
               
               
                   
                   
                   
                   
                 CAGGGCACCAAGCTAGAAATTAAG 
               
               
                   
               
               
                 hROR1 
                 61 
                 EVQLVESGGGLVQPG 
                 208 
                 GAGGTTCAGCTGGTGGAGTCTGGTGGG 
               
               
                 VH_22 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGGCTCGTACAGCCGGGTGGCTCCCTA 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 AGGCTGAGTTGCGCTGCCTCAGGCTTT 
               
               
                   
                   
                 EWVASISRGGTTYYA 
                   
                 ACCTTCTCAAGCTACGCGATGTCCTGG 
               
               
                   
                   
                 ESLEGRFTISRDDSKN 
                   
                 GTGAGACAGGCCCCTGGCAAAGGACT 
               
               
                   
                   
                 SLYLQMNSLKTEDTA 
                   
                 GGAGTGGGTGGCAAGCATTAGCCGGG 
               
               
                   
                   
                 VYYCARYDYDGYYA 
                   
                 GCGGAACTACCTATTACGCTGAGTCGT 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 TAGAGGGGCGGTTTACTATCTCCAGAG 
               
               
                   
                   
                   
                   
                 ACGATTCAAAGAACTCGTTATACTTGC 
               
               
                   
                   
                   
                   
                 AGATGAACAGCCTCAAGACCGAGGAC 
               
               
                   
                   
                   
                   
                 ACCGCCGTGTACTACTGCGCCCGGTAC 
               
               
                   
                   
                   
                   
                 GACTATGACGGGTACTATGCTATGGAT 
               
               
                   
                   
                   
                   
                 TATTGGGGACAAGGCACCCTCGTGACC 
               
               
                   
                   
                   
                   
                 GTCTCTAGC 
               
               
                   
               
               
                 hROR1 
                 62 
                 DIQMTQSPSSLSASVG 
                 209 
                 GACATCCAGATGACACAGTCCCCTTCT 
               
               
                 VL_22 
                   
                 DRVTITCKASPDINSY 
                   
                 TCACTTTCCGCTTCTGTGGGCGACAGG 
               
               
                   
                   
                 LSWYQQKPGKAPKTL 
                   
                 GTGACGATCACGTGTAAGGCCTCGCCA 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GACATTAATTCGTACTTATCGTGGTATC 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 AGCAGAAACCGGGTAAAGCTCCGAAG 
               
               
                   
                   
                 PEDFATYYCLQYDEF 
                   
                 ACTCTGATCTATAGAGCAAATAGGCTC 
               
               
                   
                   
                 PYTFGQGTKLEIK 
                   
                 GTAGACGGTGTCCCATCTAGATTTAGT 
               
               
                   
                   
                   
                   
                 GGGAGCGGCAGCGGAACCGACTTCACT 
               
               
                   
                   
                   
                   
                 CTCACCATCTCATCCCTGCAACCGGAG 
               
               
                   
                   
                   
                   
                 GATTTCGCTACTTACTATTGCTTGCAGT 
               
               
                   
                   
                   
                   
                 ATGACGAGTTTCCATATACGTTTGGTC 
               
               
                   
                   
                   
                   
                 AGGGAACCAAATTAGAGATCAAA 
               
               
                   
               
               
                 hROR1 
                 63 
                 QVTLRESGPALVKPT 
                 210 
                 CAGGTAACACTCCGAGAGAGTGGGCC 
               
               
                 VH_23 
                   
                 QTLTLTCAASGFTFSS 
                   
                 AGCTCTCGTGAAGCCCACGCAGACTTT 
               
               
                   
                   
                 YAMSWIRQPPGKALE 
                   
                 AACACTAACGTGTGCGGCAAGCGGCTT 
               
               
                   
                   
                 WLASISRGGTTYYNP 
                   
                 TACATTTTCGAGCTACGCGATGAGCTG 
               
               
                   
                   
                 SLKDRLTISKDTSANQ 
                   
                 GATAAGGCAACCTCCTGGGAAGGCGTT 
               
               
                   
                   
                 VVLKVTNMDPADTA 
                   
                 GGAGTGGTTGGCCTCAATTAGCCGGGG 
               
               
                   
                   
                 TYYCARYDYDGYYA 
                   
                 TGGCACCACTTACTACAATCCTAGTCTT 
               
               
                   
                   
                 MDYWGQGTTVTVSS 
                   
                 AAGGACAGACTTACTATTTCAAAAGAT 
               
               
                   
                   
                   
                   
                 ACGTCCGCCAACCAGGTGGTACTGAAG 
               
               
                   
                   
                   
                   
                 GTCACAAATATGGACCCAGCTGACACT 
               
               
                   
                   
                   
                   
                 GCTACTTACTACTGCGCCCGGTACGAT 
               
               
                   
                   
                   
                   
                 TACGATGGTTACTACGCTATGGATTAC 
               
               
                   
                   
                   
                   
                 TGGGGTCAAGGAACCACAGTGACCGTC 
               
               
                   
                   
                   
                   
                 AGTTCA 
               
               
                   
               
               
                 hROR1 
                 64 
                 DIQMTQSPSTLSASVG 
                 211 
                 GATATCCAGATGACGCAGTCCCCTTCA 
               
               
                 VL_23 
                   
                 DRVTITCKASPDINSY 
                   
                 ACCCTCAGTGCCAGCGTTGGTGACCGG 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTTACTATCACCTGTAAGGCTAGTCCC 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GATATAAATTCCTATTTGTCTTGGTATC 
               
               
                   
                   
                 GSGSGTAFTLTISSLQ 
                   
                 AGCAGAAGCCAGGCAAGGCTCCTAAG 
               
               
                   
                   
                 PDDFATYYCLQYDEF 
                   
                 CTGCTCATCTACCGGGCTAACAGGTTA 
               
               
                   
                   
                 PYTFGGGTKVEIK 
                   
                 GTTGACGGTGTGCCCTCCCGATTTTCCG 
               
               
                   
                   
                   
                   
                 GCAGTGGCAGCGGGACCGCTTTCACTC 
               
               
                   
                   
                   
                   
                 TTACAATCTCATCTCTTCAACCGGACG 
               
               
                   
                   
                   
                   
                 ACTTCGCTACGTACTACTGCCTCCAAT 
               
               
                   
                   
                   
                   
                 ATGATGAGTTTCCATACACATTCGGAG 
               
               
                   
                   
                   
                   
                 GAGGCACAAAAGTCGAAATCAAG 
               
               
                   
               
               
                 hROR1 
                 65 
                 EVQLVESGGGLVQPG 
                 212 
                 GAAGTCCAGCTGGTGGAGTCCGGCGGA 
               
               
                 VH_24 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCTTGGTTCAGCCCGGAGGATCTTTG 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGACTGTCTTGCGCCGCCAGCGGTTTC 
               
               
                   
                   
                 EWVSAISRGGTTYYA 
                   
                 ACTTTCAGCAGCTATGCCATGAGTTGG 
               
               
                   
                   
                 DSVKGRFTISADTSKE 
                   
                 GTTAGACAAGCTCCCGGCAAGGGGCTG 
               
               
                   
                   
                 TAYLQMNSLRAEDTA 
                   
                 GAATGGGTTAGTGCTATTAGCCGGGGA 
               
               
                   
                   
                 VYYCGRYDYDGYYA 
                   
                 GGGACAACATATTACGCTGACTCTGTC 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAAGGCCGATTCACCATCTCTGCTGAC 
               
               
                   
                   
                   
                   
                 ACGAGCAAAGAAACCGCCTACCTCCAA 
               
               
                   
                   
                   
                   
                 ATGAACAGCCTGCGAGCTGAGGACACT 
               
               
                   
                   
                   
                   
                 GCCGTCTACTATTGTGGTCGATATGATT 
               
               
                   
                   
                   
                   
                 ATGATGGGTACTATGCAATGGACTATT 
               
               
                   
                   
                   
                   
                 GGGGGCAGGGCACACTGGTGACCGTG 
               
               
                   
                   
                   
                   
                 AGCTCT 
               
               
                   
               
               
                 hROR1 
                 66 
                 DIQMTQSPSSLSASVG 
                 213 
                 GATATTCAGATGACGCAGAGTCCCTCC 
               
               
                 VL_24 
                   
                 DRVTITCKASPDINSY 
                   
                 TCCCTATCTGCCTCTGTTGGAGATCGA 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTCACCATTACGTGTAAAGCGTCTCCC 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GATATCAACAGCTACCTCTCTTGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAGCAGAAACCAGGGAAGGCCCCCAA 
               
               
                   
                   
                 PEDIATYYCLQYDEFP 
                   
                 GCTGCTGATCTATAGAGCTAATCGCTT 
               
               
                   
                   
                 YTFGQGTKLEIK 
                   
                 AGTGGATGGAGTGCCAAGCAGGTTCTC 
               
               
                   
                   
                   
                   
                 CGGGTCCGGCAGTGGAACCGATTTCAC 
               
               
                   
                   
                   
                   
                 CTTGACAATAAGTAGCTTGCAACCTGA 
               
               
                   
                   
                   
                   
                 GGATATTGCAACATACTACTGTCTACA 
               
               
                   
                   
                   
                   
                 GTACGACGAGTTCCCCTACACCTTCGG 
               
               
                   
                   
                   
                   
                 CCAAGGGACAAAGCTGGAGATTAAG 
               
               
                   
               
               
                 hROR1 
                 67 
                 EVQLVESGGGLVQPG 
                 214 
                 GAAGTGCAGCTCGTGGAGAGCGGCGG 
               
               
                 VH_25 
                   
                 GSLRLSCAASGFTFSS 
                   
                 CGGTCTGGTACAGCCAGGGGGGTCACT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 GCGTCTCTCATGTGCTGCGAGTGGCTTT 
               
               
                   
                   
                 EWVSAISRGGTTYYA 
                   
                 ACGTTCTCTTCCTACGCTATGTCCTGGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 TCAGGCAGGCACCGGGGAAGGGCTTA 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GAGTGGGTTAGTGCAATCTCTAGGGGC 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGTACAACCTACTATGCCGACTCTGTC 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAGGGCAGGTTTACAATTTCAAGAGAT 
               
               
                   
                   
                 S 
                   
                 AATTCTAAGAATACTCTTTACCTACAG 
               
               
                   
                   
                   
                   
                 ATGAATAGCTTGCGGGCGGAAGACAC 
               
               
                   
                   
                   
                   
                 AGCAGTCTATTATTGTGGCCGCTATGA 
               
               
                   
                   
                   
                   
                 CTACGACGGATACTATGCCATGGACTA 
               
               
                   
                   
                   
                   
                 CTGGGGCCAAGGCACTTTGGTCACGGT 
               
               
                   
                   
                   
                   
                 GAGCTCT 
               
               
                   
               
               
                 hROR1 
                 68 
                 DIQMTQSPSSLSASVG 
                 215 
                 GACATCCAGATGACCCAGAGCCCTAGT 
               
               
                 VL_25 
                   
                 DRVTITCKASPDINSY 
                   
                 TCATTGTCTGCCAGTGTGGGGGATAGG 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTCACTATCACGTGTAAGGCTTCCCCT 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GACATCAATTCATACCTGTCATGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAGCAGAAGCCTGGAAAAGCCCCTAA 
               
               
                   
                   
                 PEDIATYYCLQYDEFP 
                   
                 ACTGCTGATCTACCGCGCGAATAGGCT 
               
               
                   
                   
                 YTFGQGTKLEIK 
                   
                 TGTGGACGGCGTTCCAAGCCGCTTCTC 
               
               
                   
                   
                   
                   
                 TGGCTCTGGATCAGGGACCGACTTCAC 
               
               
                   
                   
                   
                   
                 CCTCACGATCTCCAGCCTCCAACCCGA 
               
               
                   
                   
                   
                   
                 GGATATCGCCACCTATTATTGCCTTCA 
               
               
                   
                   
                   
                   
                 GTACGATGAGTTCCCCTATACATTCGG 
               
               
                   
                   
                   
                   
                 CCAGGGGACAAAGCTGGAAATCAAA 
               
               
                   
               
               
                 hROR1 
                 69 
                 EVQLVESGGGLVQPG 
                 216 
                 GAGGTCCAGCTCGTCGAGTCGGGTGGG 
               
               
                 VH_26 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCTTGGTGCAACCCGGTGGCAGTTTG 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGCCTGAGCTGCGCCGCGAGCGGGTTC 
               
               
                   
                   
                 EWVSAISRGGTTYYA 
                   
                 ACTTTCAGTTCGTATGCCATGAGTTGG 
               
               
                   
                   
                 DSVKGRFTISADTSKE 
                   
                 GTGCGACAAGCGCCCGGCAAAGGACT 
               
               
                   
                   
                 TAYLQMNSLRAEDTA 
                   
                 GGAGTGGGTGTCAGCCATTAGCCGGGG 
               
               
                   
                   
                 VYYCGRYDYDGYYA 
                   
                 CGGTACTACCTACTATGCGGACTCGGT 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 CAAGGGAAGATTCACCATCAGCGCTGA 
               
               
                   
                   
                   
                   
                 TACCAGTAAGGAAACCGCTTATCTTCA 
               
               
                   
                   
                   
                   
                 GATGAACTCCCTGCGTGCCGAGGATAC 
               
               
                   
                   
                   
                   
                 AGCAGTCTACTATTGCGGGCGCTACGA 
               
               
                   
                   
                   
                   
                 TTATGACGGATATTATGCCATGGATTA 
               
               
                   
                   
                   
                   
                 CTGGGGGCAGGGCACTCTGGTCACAGT 
               
               
                   
                   
                   
                   
                 CAGCTCT 
               
               
                   
               
               
                 hROR1 
                 70 
                 DIQMTQSPSSLSASVG 
                 217 
                 GATATTCAGATGACGCAGTCTCCCTCT 
               
               
                 VL_26 
                   
                 DRVTITCQASPDINSY 
                   
                 TCCCTGAGCGCCTCCGTCGGCGATAGA 
               
               
                   
                   
                 LNWYQQKPGKAPKL 
                   
                 GTTACGATCACCTGTCAGGCCAGCCCA 
               
               
                   
                   
                 LIYRANNLETGVPSRF 
                   
                 GATATCAACTCCTATCTGAATTGGTAT 
               
               
                   
                   
                 SGSGSGTDFTLTISSL 
                   
                 CAGCAAAAGCCTGGGAAGGCTCCCAA 
               
               
                   
                   
                 QPEDIATYYCLQYDE 
                   
                 GTTGCTGATCTACAGAGCCAATAACTT 
               
               
                   
                   
                 FPYTFGQGTKLEIK 
                   
                 AGAGACTGGCGTGCCGTCTCGGTTCAG 
               
               
                   
                   
                   
                   
                 CGGGTCCGGCAGTGGAACCGACTTTAC 
               
               
                   
                   
                   
                   
                 ACTGACCATTTCCAGCCTCCAACCTGA 
               
               
                   
                   
                   
                   
                 GGATATCGCCACATATTATTGTCTCCA 
               
               
                   
                   
                   
                   
                 GTATGACGAGTTCCCTTACACATTTGG 
               
               
                   
                   
                   
                   
                 TCAAGGAACTAAACTGGAAATCAAA 
               
               
                   
               
               
                 hROR1 
                 71 
                 EVQLVESGGGLVQPG 
                 218 
                 GAGGTGCAGCTGGTCGAAAGTGGAGG 
               
               
                 VH_27 
                   
                 GSLRLSCAASGFTFSS 
                   
                 CGGACTCGTGCAGCCCGGCGGTAGTCT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 GCGATTGAGCTGTGCCGCGTCCGGCTT 
               
               
                   
                   
                 EWVSAISRGGTTYYA 
                   
                 TACTTTCTCATCTTACGCTATGAGTTGG 
               
               
                   
                   
                 DSVKGRFTISADTSKE 
                   
                 GTCCGCCAGGCCCCAGGCAAAGGACTG 
               
               
                   
                   
                 TAYLQMNSLRAEDTA 
                   
                 GAGTGGGTATCAGCCATCAGTAGGGGG 
               
               
                   
                   
                 VYYCGRYDYDGYYA 
                   
                 GGAACTACCTATTACGCAGATTCTGTG 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAGGGACGCTTCACCATCAGCGCGGAC 
               
               
                   
                   
                   
                   
                 ACTAGCAAGGAGACTGCCTACCTGCAA 
               
               
                   
                   
                   
                   
                 ATGAATAGTCTGAGAGCCGAGGATACC 
               
               
                   
                   
                   
                   
                 GCCGTGTACTATTGTGGCAGGTATGAC 
               
               
                   
                   
                   
                   
                 TACGATGGCTATTATGCTATGGATTAC 
               
               
                   
                   
                   
                   
                 TGGGGCCAGGGGACGTTAGTGACAGTA 
               
               
                   
                   
                   
                   
                 AGCTCT 
               
               
                   
               
               
                 hROR1 
                 72 
                 DIQMTQSPSSLSASVG 
                 219 
                 GATATTCAGATGACCCAATCCCCTTCTT 
               
               
                 VL_27 
                   
                 DRVTITCRASPDINSY 
                   
                 CTCTGAGCGCTTCTGTGGGCGATAGAG 
               
               
                   
                   
                 VAWYQQKPGKAPKL 
                   
                 TTACAATAACCTGTCGGGCGTCCCCAG 
               
               
                   
                   
                 LIYRANFLESGVPSRF 
                   
                 ACATTAACTCTTATGTAGCATGGTATC 
               
               
                   
                   
                 SGSRSGTDFTLTISSL 
                   
                 AGCAAAAGCCTGGAAAGGCACCAAAG 
               
               
                   
                   
                 QPEDFATYYCLQYDE 
                   
                 TTACTGATCTACCGGGCCAATTTTCTGG 
               
               
                   
                   
                 FPYTFGQGTKVEIK 
                   
                 AGTCGGGCGTGCCCTCACGATTTAGCG 
               
               
                   
                   
                   
                   
                 GTAGCAGATCAGGCACAGACTTTACTC 
               
               
                   
                   
                   
                   
                 TGACCATTAGCTCTCTGCAACCCGAGG 
               
               
                   
                   
                   
                   
                 ACTTCGCCACCTACTACTGTTTGCAGTA 
               
               
                   
                   
                   
                   
                 TGACGAGTTTCCATACACTTTTGGTCA 
               
               
                   
                   
                   
                   
                 AGGAACCAAAGTCGAAATCAAA 
               
               
                   
               
               
                 hROR1 
                 73 
                 QIQLVQSGAEVKKPG 
                 220 
                 CAGATACAGCTGGTGCAGTCTGGTGCC 
               
               
                 VH_28 
                   
                 ASVKVSCAASGFTFSS 
                   
                 GAGGTTAAAAAGCCCGGAGCCTCGGTT 
               
               
                   
                   
                 YAMSWVRQAPGKSF 
                   
                 AAAGTGAGTTGTGCGGCAAGCGGATTC 
               
               
                   
                   
                 KWMGSISRGGTTYYS 
                   
                 ACGTTCAGTTCCTACGCTATGTCCTGG 
               
               
                   
                   
                 ADFKGRFAITKDTSAS 
                   
                 GTGCGGCAGGCTCCTGGCAAGTCATTT 
               
               
                   
                   
                 TAYMELSSLRSEDTA 
                   
                 AAGTGGATGGGGTCGATCTCACGGGGT 
               
               
                   
                   
                 VYYCARYDYDGYYA 
                   
                 GGAACCACCTATTACTCTGCCGACTTC 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAGGGGAGATTTGCGATTACAAAAGAT 
               
               
                   
                   
                   
                   
                 ACAAGCGCCTCTACGGCCTACATGGAG 
               
               
                   
                   
                   
                   
                 TTAAGTAGCCTTAGAAGCGAAGACACG 
               
               
                   
                   
                   
                   
                 GCGGTGTACTACTGCGCCAGATATGAC 
               
               
                   
                   
                   
                   
                 TATGACGGCTACTACGCCATGGACTAC 
               
               
                   
                   
                   
                   
                 TGGGGCCAGGGCACACTGGTTACAGTC 
               
               
                   
                   
                   
                   
                 AGCTCT 
               
               
                   
               
               
                 hROR1 
                 74 
                 DIVMTQSPDSLAVSL 
                 221 
                 GATATCGTGATGACACAAAGCCCAGAC 
               
               
                 VL_28 
                   
                 GERATISCKASPDINS 
                   
                 AGTCTGGCAGTGTCCCTCGGCGAGCGC 
               
               
                   
                   
                 YLSWYQQKPGQPPKL 
                   
                 GCTACCATCTCATGCAAAGCTAGTCCC 
               
               
                   
                   
                 LIYRANRLVDGVPDR 
                   
                 GACATCAATTCCTATCTGTCCTGGTATC 
               
               
                   
                   
                 FSGSGSRTDFTLTISSL 
                   
                 AGCAAAAACCAGGCCAACCCCCCAAG 
               
               
                   
                   
                 QAEDVAVYYCLQYD 
                   
                 CTGCTTATCTATCGGGCTAACCGATTA 
               
               
                   
                   
                 EFPYTFGQGTKVEIK 
                   
                 GTCGATGGGGTGCCAGATAGATTTTCA 
               
               
                   
                   
                   
                   
                 GGCTCTGGTTCCCGGACAGATTTTACT 
               
               
                   
                   
                   
                   
                 CTCACGATCTCCTCACTACAGGCAGAA 
               
               
                   
                   
                   
                   
                 GATGTTGCAGTGTATTACTGCCTGCAA 
               
               
                   
                   
                   
                   
                 TACGACGAGTTCCCCTACACCTTCGGC 
               
               
                   
                   
                   
                   
                 CAAGGCACGAAAGTGGAGATCAAG 
               
               
                   
               
               
                 hROR1 
                 75 
                 EVQLVESGGGLVQPG 
                 222 
                 GAAGTGCAGCTGGTGGAGTCTGGCGGC 
               
               
                 (VH-VL)_14.CD8a(3x).CD28z 
                   
                 GSLRLSCATSGFTFSS 
                   
                 GGTCTGGTGCAGCCCGGCGGCTCTCTG 
               
               
                   
                   
                 YAMSWMRQAPGKGL 
                   
                 CGCCTCTCCTGTGCCACCTCTGGTTTTA 
               
               
                   
                   
                 EWVASISRGGTTYYA 
                   
                 CATTCTCCTCCTACGCTATGTCCTGGAT 
               
               
                   
                   
                 DSVKGRFTISVDKSK 
                   
                 GCGGCAAGCCCCCGGCAAGGGCCTAG 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 AGTGGGTCGCCTCAATCAGCAGGGGCG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGACGACTTATTATGCCGATTCAGTTA 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AGGGGAGATTCACAATTTCCGTGGATA 
               
               
                   
                   
                 SGGGGSGGGGSGGG 
                   
                 AATCCAAGAATACCTTATACCTCCAGA 
               
               
                   
                   
                 GSDIQMTQSPSSLSAS 
                   
                 TGAACTCTCTGCGGGCCGAAGATACGG 
               
               
                   
                   
                 VGDRVTITCKASPDIN 
                   
                 CCGTATATTATTGTGGGAGGTATGACT 
               
               
                   
                   
                 SYLNWYQQKPGKAP 
                   
                 ACGACGGATATTACGCCATGGATTATT 
               
               
                   
                   
                 KLLIYRANRLVDGVP 
                   
                 GGGGGCAGGGGACACTTGTTACAGTGA 
               
               
                   
                   
                 SRFSGSGSGTDYTLTI 
                   
                 GTTCCGGTGGTGGGGGGTCTGGAGGCG 
               
               
                   
                   
                 SSLQPEDFATYYCLQ 
                   
                 GGGGCAGTGGAGGCGGAGGGTCTGAT 
               
               
                   
                   
                 YDEFPYTFGAGTKVEI 
                   
                 ATACAGATGACACAGAGCCCTTCAAGT 
               
               
                   
                   
                 KKPTTTPAPRPPTPAP 
                   
                 TTATCTGCAAGCGTCGGCGATCGTGTT 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 ACAATAACTTGCAAGGCATCTCCCGAC 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 ATCAATTCCTACCTCAACTGGTATCAG 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 CAGAAGCCTGGGAAGGCTCCTAAGCTG 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 CTTATTTACAGAGCAAATCGCCTGGTG 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 GACGGCGTGCCCAGTCGGTTTTCCGGG 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 TCTGGGAGCGGAACGGATTACACACTG 
               
               
                   
                   
                 TIASQPLSLRPEACRP 
                   
                 ACCATCTCAAGCCTGCAACCCGAAGAC 
               
               
                   
                   
                 AAGGAVHTRGLDFA 
                   
                 TTCGCTACATATTACTGCCTTCAGTATG 
               
               
                   
                   
                 CDIYIWAPLAGTCGV 
                   
                 ATGAGTTCCCATATACCTTCGGCGCTG 
               
               
                   
                   
                 LLLSLVITLYCNHRNR 
                   
                 GGACCAAGGTGGAGATAAAGAAGCCT 
               
               
                   
                   
                 SKRSRGGHSDYMNM 
                   
                 ACCACCACCCCCGCACCTCGTCCTCCA 
               
               
                   
                   
                 TPRRPGPTRKHYQPY 
                   
                 ACCCCTGCACCTACGATTGCCAGTCAG 
               
               
                   
                   
                 APPRDFAAYRSRVKF 
                   
                 CCTCTTTCACTGCGGCCTGAGGCCAGC 
               
               
                   
                   
                 SRSADAPAYQQGQN 
                   
                 AGACCAGCTGCCGGCGGTGCCGTCCAT 
               
               
                   
                   
                 QLYNELNLGRREEYD 
                   
                 ACAAGAGGACTGGACTTCGCGTCCGAT 
               
               
                   
                   
                 VLDKRRGRDPEMGG 
                   
                 AAACCTACTACCACTCCAGCCCCAAGG 
               
               
                   
                   
                 KPRRKNPQEGLYNEL 
                   
                 CCCCCAACCCCAGCACCGACTATCGCA 
               
               
                   
                   
                 QKDKMAEAYSEIGM 
                   
                 TCACAGCCTTTGTCACTGCGTCCTGAA 
               
               
                   
                   
                 KGERRRGKGHDGLY 
                   
                 GCCAGCCGGCCAGCTGCAGGGGGGGC 
               
               
                   
                   
                 QGLSTATKDTYDALH 
                   
                 CGTCCACACAAGGGGACTCGACTTTGC 
               
               
                   
                   
                 MQALPPR 
                   
                 GAGTGATAAGCCCACCACCACCCCTGC 
               
               
                   
                   
                   
                   
                 CCCTAGACCTCCAACCCCAGCCCCTAC 
               
               
                   
                   
                   
                   
                 AATCGCCAGCCAGCCCCTGAGCCTGAG 
               
               
                   
                   
                   
                   
                 GCCCGAAGCCTGTAGACCTGCCGCTGG 
               
               
                   
                   
                   
                   
                 CGGAGCCGTGCACACCAGAGGCCTGG 
               
               
                   
                   
                   
                   
                 ATTTCGCCTGCGACATCTACATCTGGG 
               
               
                   
                   
                   
                   
                 CCCCTCTGGCCGGCACCTGTGGCGTGC 
               
               
                   
                   
                   
                   
                 TGCTGCTGAGCCTGGTCATCACCCTGT 
               
               
                   
                   
                   
                   
                 ACTGCAACCACCGGAATAGGAGCAAG 
               
               
                   
                   
                   
                   
                 CGGAGCAGAGGCGGCCACAGCGACTA 
               
               
                   
                   
                   
                   
                 CATGAACATGACCCCCCGGAGGCCTGG 
               
               
                   
                   
                   
                   
                 CCCCACCCGGAAGCACTACCAGCCCTA 
               
               
                   
                   
                   
                   
                 CGCCCCTCCCAGGGACTTCGCCGCCTA 
               
               
                   
                   
                   
                   
                 CCGGAGCCGGGTGAAGTTCAGCCGGA 
               
               
                   
                   
                   
                   
                 GCGCCGACGCCCCTGCCTACCAGCAGG 
               
               
                   
                   
                   
                   
                 GCCAGAACCAGCTGTACAACGAGCTGA 
               
               
                   
                   
                   
                   
                 ACCTGGGCCGGAGGGAGGAGTACGAC 
               
               
                   
                   
                   
                   
                 GTGCTGGACAAGCGGAGAGGCCGGGA 
               
               
                   
                   
                   
                   
                 CCCTGAGATGGGCGGCAAGCCCCGGA 
               
               
                   
                   
                   
                   
                 GAAAGAACCCTCAGGAGGGCCTGTATA 
               
               
                   
                   
                   
                   
                 ACGAACTGCAGAAAGACAAGATGGCC 
               
               
                   
                   
                   
                   
                 GAGGCCTACAGCGAGATCGGCATGAA 
               
               
                   
                   
                   
                   
                 GGGCGAGCGGCGGAGGGGCAAGGGCC 
               
               
                   
                   
                   
                   
                 ACGACGGCCTGTACCAGGGCCTGAGCA 
               
               
                   
                   
                   
                   
                 CCGCCACCAAGGATACCTACGACGCCC 
               
               
                   
                   
                   
                   
                 TGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 hROR1 
                 76 
                 DIQMTQSPSSLSASVG 
                 223 
                 GATATTCAGATGACCCAGTCACCTTCG 
               
               
                 (VL-VH)_05.CD8a(3x).CD28z 
                   
                 DRVTITCKASPDINSY 
                   
                 AGTCTGAGCGCATCCGTGGGCGACAGA 
               
               
                   
                   
                 LSWYQQKPGKAPKLL 
                   
                 GTGACCATTACCTGTAAGGCCAGCCCG 
               
               
                   
                   
                 IYRANRLVDGVPSRFS 
                   
                 GACATTAACAGCTACCTATCGTGGTAT 
               
               
                   
                   
                 GSGSGTDFTLTISSLQ 
                   
                 CAGCAAAAGCCTGGTAAGGCCCCTAAA 
               
               
                   
                   
                 PEDIATYYCLQYDEFP 
                   
                 CTCCTTATCTACAGGGCTAATAGGTTG 
               
               
                   
                   
                 YTFGQGTKLEIKGGG 
                   
                 GTAGACGGGGTGCCTAGCCGGTTCTCT 
               
               
                   
                   
                 GSGGGGSGGGGSEVQ 
                   
                 GGTTCCGGCAGCGGTACGGACTTTACT 
               
               
                   
                   
                 LVESGGGLVQPGGSL 
                   
                 CTGACCATAAGCTCTCTGCAACCAGAA 
               
               
                   
                   
                 RLSCAASGFTFSSYA 
                   
                 GACATCGCAACATACTACTGTTTACAA 
               
               
                   
                   
                 MSWVRQAPGKGLEW 
                   
                 TACGACGAATTTCCTTATACCTTTGGCC 
               
               
                   
                   
                 VSSISRGGTTYYPDSV 
                   
                 AGGGGACCAAGTTAGAGATCAAGGGG 
               
               
                   
                   
                 KGRFTISRDNSKNTLY 
                   
                 GGCGGCGGAAGTGGTGGAGGGGGAAG 
               
               
                   
                   
                 LQMNSLRAEDTAVY 
                   
                 TGGTGGAGGAGGAAGCGAAGTGCAAC 
               
               
                   
                   
                 YCGRYDYDGYYAMD 
                   
                 TGGTCGAGTCTGGGGGCGGCCTTGTGC 
               
               
                   
                   
                 YWGQGTLVTVSSKPT 
                   
                 AACCTGGAGGCAGCCTTCGACTCAGTT 
               
               
                   
                   
                 TTPAPRPPTPAPTIASQ 
                   
                 GCGCCGCGTCTGGTTTTACCTTCTCCTC 
               
               
                   
                   
                 PLSLRPEASRPAAGG 
                   
                 TTACGCGATGAGCTGGGTTCGCCAGGC 
               
               
                   
                   
                 AVHTRGLDFASDKPT 
                   
                 CCCCGGCAAGGGACTTGAGTGGGTTAG 
               
               
                   
                   
                 TTPAPRPPTPAPTIASQ 
                   
                 TTCGATCTCCCGCGGAGGCACCACATA 
               
               
                   
                   
                 PLSLRPEASRPAAGG 
                   
                 TTATCCTGACTCGGTTAAGGGACGCTT 
               
               
                   
                   
                 AVHTRGLDFASDKPT 
                   
                 CACTATCTCTAGGGACAATTCAAAGAA 
               
               
                   
                   
                 TTPAPRPPTPAPTIASQ 
                   
                 CACACTGTATCTCCAAATGAACTCCTT 
               
               
                   
                   
                 PLSLRPEACRPAAGG 
                   
                 GCGGGCCGAGGACACTGCTGTGTATTA 
               
               
                   
                   
                 AVHTRGLDFACDIYI 
                   
                 TTGCGGACGATACGACTACGATGGGTA 
               
               
                   
                   
                 WAPLAGTCGVLLLSL 
                   
                 TTACGCCATGGATTACTGGGGGCAAGG 
               
               
                   
                   
                 VITLYCNHRNRSKRS 
                   
                 TACACTGGTCACTGTGAGTTCGAAGCC 
               
               
                   
                   
                 RGGHSDYMNMTPRR 
                   
                 TACCACCACCCCCGCACCTCGTCCTCC 
               
               
                   
                   
                 PGPTRKHYQPYAPPR 
                   
                 AACCCCTGCACCTACGATTGCCAGTCA 
               
               
                   
                   
                 DFAAYRSRVKFSRSA 
                   
                 GCCTCTTTCACTGCGGCCTGAGGCCAG 
               
               
                   
                   
                 DAPAYQQGQNQLYN 
                   
                 CAGACCAGCTGCCGGCGGTGCCGTCCA 
               
               
                   
                   
                 ELNLGRREEYDVLDK 
                   
                 TACAAGAGGACTGGACTTCGCGTCCGA 
               
               
                   
                   
                 RRGRDPEMGGKPRR 
                   
                 TAAACCTACTACCACTCCAGCCCCAAG 
               
               
                   
                   
                 KNPQEGLYNELQKDK 
                   
                 GCCCCCAACCCCAGCACCGACTATCGC 
               
               
                   
                   
                 MAEAYSEIGMKGERR 
                   
                 ATCACAGCCTTTGTCACTGCGTCCTGA 
               
               
                   
                   
                 RGKGHDGLYQGLST 
                   
                 AGCCAGCCGGCCAGCTGCAGGGGGGG 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 CCGTCCACACAAGGGGACTCGACTTTG 
               
               
                   
                   
                 PPR 
                   
                 CGAGTGATAAGCCCACCACCACCCCTG 
               
               
                   
                   
                   
                   
                 CCCCTAGACCTCCAACCCCAGCCCCTA 
               
               
                   
                   
                   
                   
                 CAATCGCCAGCCAGCCCCTGAGCCTGA 
               
               
                   
                   
                   
                   
                 GGCCCGAAGCCTGTAGACCTGCCGCTG 
               
               
                   
                   
                   
                   
                 GCGGAGCCGTGCACACCAGAGGCCTG 
               
               
                   
                   
                   
                   
                 GATTTCGCCTGCGACATCTACATCTGG 
               
               
                   
                   
                   
                   
                 GCCCCTCTGGCCGGCACCTGTGGCGTG 
               
               
                   
                   
                   
                   
                 CTGCTGCTGAGCCTGGTCATCACCCTG 
               
               
                   
                   
                   
                   
                 TACTGCAACCACCGGAATAGGAGCAA 
               
               
                   
                   
                   
                   
                 GCGGAGCAGAGGCGGCCACAGCGACT 
               
               
                   
                   
                   
                   
                 ACATGAACATGACCCCCCGGAGGCCTG 
               
               
                   
                   
                   
                   
                 GCCCCACCCGGAAGCACTACCAGCCCT 
               
               
                   
                   
                   
                   
                 ACGCCCCTCCCAGGGACTTCGCCGCCT 
               
               
                   
                   
                   
                   
                 ACCGGAGCCGGGTGAAGTTCAGCCGG 
               
               
                   
                   
                   
                   
                 AGCGCCGACGCCCCTGCCTACCAGCAG 
               
               
                   
                   
                   
                   
                 GGCCAGAACCAGCTGTACAACGAGCTG 
               
               
                   
                   
                   
                   
                 AACCTGGGCCGGAGGGAGGAGTACGA 
               
               
                   
                   
                   
                   
                 CGTGCTGGACAAGCGGAGAGGCCGGG 
               
               
                   
                   
                   
                   
                 ACCCTGAGATGGGCGGCAAGCCCCGG 
               
               
                   
                   
                   
                   
                 AGAAAGAACCCTCAGGAGGGCCTGTAT 
               
               
                   
                   
                   
                   
                 AACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGA 
               
               
                   
                   
                   
                   
                 AGGGCGAGCGGCGGAGGGGCAAGGGC 
               
               
                   
                   
                   
                   
                 CACGACGGCCTGTACCAGGGCCTGAGC 
               
               
                   
                   
                   
                   
                 ACCGCCACCAAGGATACCTACGACGCC 
               
               
                   
                   
                   
                   
                 CTGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
                   
                   
                   
                 TGA 
               
               
                   
               
               
                 hROR1 
                 77 
                 EVQLVESGGGLVQPG 
                 224 
                 GAGGTTCAACTTGTGGAATCCGGCGGC 
               
               
                 (VH-VL)_14-3.CD8a(3x).CD28z 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGGTTAGTCCAGCCCGGCGGGAGCTTG 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGGCTGTCCTGCGCCGCCTCTGGATTC 
               
               
                   
                   
                 EWVASISRGGTTYYA 
                   
                 ACTTTTAGCTCCTATGCTATGTCTTGGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 TAAGGCAGGCCCCTGGTAAAGGACTAG 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 AGTGGGTGGCCTCGATCTCCCGTGGTG 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GCACTACATACTACGCCGACTCCGTTA 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAGGCCGGTTTACCATCTCCCGTGACA 
               
               
                   
                   
                 SGGGGSGGGGSGGG 
                   
                 ACTCTAAAAATACTTTGTACCTGCAAA 
               
               
                   
                   
                 GSDIQMTQSPSSLSAS 
                   
                 TGAACTCCCTGCGGGCAGAAGACACAG 
               
               
                   
                   
                 VGDRVTITCKASPDIN 
                   
                 CCGTGTACTATTGCGGGCGTTACGATT 
               
               
                   
                   
                 SYLNWYQQKPGKAP 
                   
                 ACGACGGATATTACGCAATGGACTACT 
               
               
                   
                   
                 KLLIYRANRLVDGVP 
                   
                 GGGGCCAGGGCACACTGGTCACCGTGA 
               
               
                   
                   
                 SRFSGSGSGTDFTLTIS 
                   
                 GCAGCGGGGGCGGAGGAAGTGGAGGA 
               
               
                   
                   
                 SLQPEDIATYYCLQY 
                   
                 GGCGGTAGTGGTGGGGGAGGAAGCGA 
               
               
                   
                   
                 DEFPYTFGGGTKVEIK 
                   
                 TATACAAATGACTCAGTCCCCTAGTAG 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 CCTTAGTGCTAGTGTGGGAGACAGAGT 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 GACCATCACCTGCAAAGCATCTCCTGA 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 TATCAATTCCTACCTTAACTGGTATCAA 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 CAGAAGCCTGGCAAAGCTCCAAAGCTC 
               
               
                   
                   
                 SQPLSLRPEASRPAAG 
                   
                 CTGATTTATCGCGCGAACAGATTGGTC 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 GATGGGGTCCCTTCCAGATTCAGCGGC 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 TCAGGGTCAGGGACCGATTTCACCCTC 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 ACAATTAGTTCACTTCAGCCCGAGGAC 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 ATCGCCACGTATTATTGCCTTCAGTAC 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 GATGAGTTCCCTTACACCTTTGGCGGG 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 GGAACTAAAGTCGAAATTAAGAAGCCT 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 ACCACCACCCCCGCACCTCGTCCTCCA 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 ACCCCTGCACCTACGATTGCCAGTCAG 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 CCTCTTTCACTGCGGCCTGAGGCCAGC 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 AGACCAGCTGCCGGCGGTGCCGTCCAT 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 ACAAGAGGACTGGACTTCGCGTCCGAT 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 AAACCTACTACCACTCCAGCCCCAAGG 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 CCCCCAACCCCAGCACCGACTATCGCA 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 TCACAGCCTTTGTCACTGCGTCCTGAA 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 GCCAGCCGGCCAGCTGCAGGGGGGGC 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 CGTCCACACAAGGGGACTCGACTTTGC 
               
               
                   
                   
                 PPR 
                   
                 GAGTGATAAGCCCACCACCACCCCTGC 
               
               
                   
                   
                   
                   
                 CCCTAGACCTCCAACCCCAGCCCCTAC 
               
               
                   
                   
                   
                   
                 AATCGCCAGCCAGCCCCTGAGCCTGAG 
               
               
                   
                   
                   
                   
                 GCCCGAAGCCTGTAGACCTGCCGCTGG 
               
               
                   
                   
                   
                   
                 CGGAGCCGTGCACACCAGAGGCCTGG 
               
               
                   
                   
                   
                   
                 ATTTCGCCTGCGACATCTACATCTGGG 
               
               
                   
                   
                   
                   
                 CCCCTCTGGCCGGCACCTGTGGCGTGC 
               
               
                   
                   
                   
                   
                 TGCTGCTGAGCCTGGTCATCACCCTGT 
               
               
                   
                   
                   
                   
                 ACTGCAACCACCGGAATAGGAGCAAG 
               
               
                   
                   
                   
                   
                 CGGAGCAGAGGCGGCCACAGCGACTA 
               
               
                   
                   
                   
                   
                 CATGAACATGACCCCCCGGAGGCCTGG 
               
               
                   
                   
                   
                   
                 CCCCACCCGGAAGCACTACCAGCCCTA 
               
               
                   
                   
                   
                   
                 CGCCCCTCCCAGGGACTTCGCCGCCTA 
               
               
                   
                   
                   
                   
                 CCGGAGCCGGGTGAAGTTCAGCCGGA 
               
               
                   
                   
                   
                   
                 GCGCCGACGCCCCTGCCTACCAGCAGG 
               
               
                   
                   
                   
                   
                 GCCAGAACCAGCTGTACAACGAGCTGA 
               
               
                   
                   
                   
                   
                 ACCTGGGCCGGAGGGAGGAGTACGAC 
               
               
                   
                   
                   
                   
                 GTGCTGGACAAGCGGAGAGGCCGGGA 
               
               
                   
                   
                   
                   
                 CCCTGAGATGGGCGGCAAGCCCCGGA 
               
               
                   
                   
                   
                   
                 GAAAGAACCCTCAGGAGGGCCTGTATA 
               
               
                   
                   
                   
                   
                 ACGAACTGCAGAAAGACAAGATGGCC 
               
               
                   
                   
                   
                   
                 GAGGCCTACAGCGAGATCGGCATGAA 
               
               
                   
                   
                   
                   
                 GGGCGAGCGGCGGAGGGGCAAGGGCC 
               
               
                   
                   
                   
                   
                 ACGACGGCCTGTACCAGGGCCTGAGCA 
               
               
                   
                   
                   
                   
                 CCGCCACCAAGGATACCTACGACGCCC 
               
               
                   
                   
                   
                   
                 TGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 hROR1 
                 78 
                 EVQLVESGGGLVQPG 
                 225 
                 GAAGTGCAGCTTGTGGAGTCAGGAGG 
               
               
                 (VH-VL)_14-4.CD8a(3x).CD28z 
                   
                 GSLRLSCAASGFTFSS 
                   
                 AGGGCTAGTTCAGCCAGGCGGCTCTCT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 GAGACTATCTTGTGCTGCCTCCGGCTTC 
               
               
                   
                   
                 EWVASISRGGTTYYP 
                   
                 ACATTTAGCTCTTATGCAATGTCCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNVR 
                   
                 GTCCGCCAGGCCCCTGGTAAAGGCCTG 
               
               
                   
                   
                 NILYLQMSSLRSEDTA 
                   
                 GAATGGGTTGCTTCTATCTCTAGAGGC 
               
               
                   
                   
                 MYYCGRYDYDGYYA 
                   
                 GGAACCACTTACTACCCTGATTCAGTG 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AAGGGGAGATTCACAATTAGTAGGGA 
               
               
                   
                   
                 GGGGSGGGGSGGGG 
                   
                 CAACGTGCGGAACATCCTCTACCTACA 
               
               
                   
                   
                 SDIQMTQSPSSLSASV 
                   
                 GATGTCAAGTTTACGCAGTGAGGACAC 
               
               
                   
                   
                 GDRVTITCKASPDINS 
                   
                 TGCGATGTATTACTGCGGTCGATACGA 
               
               
                   
                   
                 YLNWYQQKPGKAPK 
                   
                 TTATGATGGATATTATGCAATGGATTA 
               
               
                   
                   
                 LLIYRANRLVDGVPS 
                   
                 TTGGGGCCAGGGCACTCTGGTCACAGT 
               
               
                   
                   
                 RFSGSGSGTDYTLTIS 
                   
                 ATCTTCCGGCGGCGGTGGTTCTGGCGG 
               
               
                   
                   
                 SLQPEDFATYYCLQY 
                   
                 TGGTGGAAGCGGAGGGGGGGGGTCCG 
               
               
                   
                   
                 DEFPYTFGAGTKVEIK 
                   
                 ACATCCAGATGACCCAATCACCATCGA 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 GTCTTAGTGCATCCGTTGGGGATAGAG 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 TGACAATCACTTGTAAGGCATCCCCGG 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 ACATCAACTCATATCTTAATTGGTATC 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 AGCAAAAGCCGGGCAAGGCCCCTAAG 
               
               
                   
                   
                 SQPLSLRPEASRPAAG 
                   
                 CTCCTGATTTATAGGGCCAACCGCCTT 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 GTGGATGGAGTCCCCTCCCGCTTTAGT 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 GGAAGCGGCTCTGGCACAGACTACACC 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 CTGACTATCAGCTCCTTGCAGCCTGAG 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 GATTTTGCTACCTACTACTGTCTTCAGT 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 ACGATGAATTTCCATACACTTTCGGTG 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 CTGGGACAAAAGTGGAGATCAAAAAG 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 CCTACCACCACCCCCGCACCTCGTCCT 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 CCAACCCCTGCACCTACGATTGCCAGT 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 CAGCCTCTTTCACTGCGGCCTGAGGCC 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 AGCAGACCAGCTGCCGGCGGTGCCGTC 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 CATACAAGAGGACTGGACTTCGCGTCC 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 GATAAACCTACTACCACTCCAGCCCCA 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 AGGCCCCCAACCCCAGCACCGACTATC 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 GCATCACAGCCTTTGTCACTGCGTCCT 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 GAAGCCAGCCGGCCAGCTGCAGGGGG 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 GGCCGTCCACACAAGGGGACTCGACTT 
               
               
                   
                   
                 PPR 
                   
                 TGCGAGTGATAAGCCCACCACCACCCC 
               
               
                   
                   
                   
                   
                 TGCCCCTAGACCTCCAACCCCAGCCCC 
               
               
                   
                   
                   
                   
                 TACAATCGCCAGCCAGCCCCTGAGCCT 
               
               
                   
                   
                   
                   
                 GAGGCCCGAAGCCTGTAGACCTGCCGC 
               
               
                   
                   
                   
                   
                 TGGCGGAGCCGTGCACACCAGAGGCCT 
               
               
                   
                   
                   
                   
                 GGATTTCGCCTGCGACATCTACATCTG 
               
               
                   
                   
                   
                   
                 GGCCCCTCTGGCCGGCACCTGTGGCGT 
               
               
                   
                   
                   
                   
                 GCTGCTGCTGAGCCTGGTCATCACCCT 
               
               
                   
                   
                   
                   
                 GTACTGCAACCACCGGAATAGGAGCA 
               
               
                   
                   
                   
                   
                 AGCGGAGCAGAGGCGGCCACAGCGAC 
               
               
                   
                   
                   
                   
                 TACATGAACATGACCCCCCGGAGGCCT 
               
               
                   
                   
                   
                   
                 GGCCCCACCCGGAAGCACTACCAGCCC 
               
               
                   
                   
                   
                   
                 TACGCCCCTCCCAGGGACTTCGCCGCC 
               
               
                   
                   
                   
                   
                 TACCGGAGCCGGGTGAAGTTCAGCCGG 
               
               
                   
                   
                   
                   
                 AGCGCCGACGCCCCTGCCTACCAGCAG 
               
               
                   
                   
                   
                   
                 GGCCAGAACCAGCTGTACAACGAGCTG 
               
               
                   
                   
                   
                   
                 AACCTGGGCCGGAGGGAGGAGTACGA 
               
               
                   
                   
                   
                   
                 CGTGCTGGACAAGCGGAGAGGCCGGG 
               
               
                   
                   
                   
                   
                 ACCCTGAGATGGGCGGCAAGCCCCGG 
               
               
                   
                   
                   
                   
                 AGAAAGAACCCTCAGGAGGGCCTGTAT 
               
               
                   
                   
                   
                   
                 AACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGA 
               
               
                   
                   
                   
                   
                 AGGGCGAGCGGCGGAGGGGCAAGGGC 
               
               
                   
                   
                   
                   
                 CACGACGGCCTGTACCAGGGCCTGAGC 
               
               
                   
                   
                   
                   
                 ACCGCCACCAAGGATACCTACGACGCC 
               
               
                   
                   
                   
                   
                 CTGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 hROR1 
                 79 
                 EVQLVESGGGLVQPG 
                 226 
                 GAAGTGCAACTGGTCGAGTCTGGGGGC 
               
               
                 (VH_5-VL_14).CD8a(3x).CD28z 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCCTTGTGCAACCTGGAGGCAGCCTT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGACTCAGTTGCGCCGCGTCTGGTTTT 
               
               
                   
                   
                 EWVSSISRGGTTYYP 
                   
                 ACCTTCTCCTCTTACGCGATGAGCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 GTTCGCCAGGCCCCCGGCAAGGGACTT 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GAGTGGGTTAGTTCGATCTCCCGCGGA 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGCACCACATATTATCCTGACTCGGTT 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAGGGACGCTTCACTATCTCTAGGGAC 
               
               
                   
                   
                 SGGGGSGGGGSGGG 
                   
                 AATTCAAAGAACACACTGTATCTCCAA 
               
               
                   
                   
                 GSDIQMTQSPSSLSAS 
                   
                 ATGAACTCCTTGCGGGCCGAGGACACT 
               
               
                   
                   
                 VGDRVTITCKASPDIN 
                   
                 GCTGTGTATTATTGCGGACGATACGAC 
               
               
                   
                   
                 SYLNWYQQKPGKAP 
                   
                 TACGATGGGTATTACGCCATGGATTAC 
               
               
                   
                   
                 KLLIYRANRLVDGVP 
                   
                 TGGGGGCAAGGTACACTGGTCACTGTG 
               
               
                   
                   
                 SRFSGSGSGTDYTLTI 
                   
                 AGTTCGGGGGGCGGCGGAAGTGGTGG 
               
               
                   
                   
                 SSLQPEDFATYYCLQ 
                   
                 AGGGGGAAGTGGTGGAGGAGGAAGCG 
               
               
                   
                   
                 YDEFPYTFGAGTKVEI 
                   
                 ATATACAGATGACACAGAGCCCTTCAA 
               
               
                   
                   
                 KKPTTTPAPRPPTPAP 
                   
                 GTTTATCTGCAAGCGTCGGCGATCGTG 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 TTACAATAACTTGCAAGGCATCTCCCG 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 ACATCAATTCCTACCTCAACTGGTATC 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 AGCAGAAGCCTGGGAAGGCTCCTAAG 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 CTGCTTATTTACAGAGCAAATCGCCTG 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 GTGGACGGCGTGCCCAGTCGGTTTTCC 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 GGGTCTGGGAGCGGAACGGATTACAC 
               
               
                   
                   
                 TIASQPLSLRPEACRP 
                   
                 ACTGACCATCTCAAGCCTGCAACCCGA 
               
               
                   
                   
                 AAGGAVHTRGLDFA 
                   
                 AGACTTCGCTACATATTACTGCCTTCA 
               
               
                   
                   
                 CDIYIWAPLAGTCGV 
                   
                 GTATGATGAGTTCCCATATACCTTCGG 
               
               
                   
                   
                 LLLSLVITLYCNHRNR 
                   
                 CGCTGGGACCAAGGTGGAGATAAAGA 
               
               
                   
                   
                 SKRSRGGHSDYMNM 
                   
                 AGCCTACCACCACCCCCGCACCTCGTC 
               
               
                   
                   
                 TPRRPGPTRKHYQPY 
                   
                 CTCCAACCCCTGCACCTACGATTGCCA 
               
               
                   
                   
                 APPRDFAAYRSRVKF 
                   
                 GTCAGCCTCTTTCACTGCGGCCTGAGG 
               
               
                   
                   
                 SRSADAPAYQQGQN 
                   
                 CCAGCAGACCAGCTGCCGGCGGTGCCG 
               
               
                   
                   
                 QLYNELNLGRREEYD 
                   
                 TCCATACAAGAGGACTGGACTTCGCGT 
               
               
                   
                   
                 VLDKRRGRDPEMGG 
                   
                 CCGATAAACCTACTACCACTCCAGCCC 
               
               
                   
                   
                 KPRRKNPQEGLYNEL 
                   
                 CAAGGCCCCCAACCCCAGCACCGACTA 
               
               
                   
                   
                 QKDKMAEAYSEIGM 
                   
                 TCGCATCACAGCCTTTGTCACTGCGTCC 
               
               
                   
                   
                 KGERRRGKGHDGLY 
                   
                 TGAAGCCAGCCGGCCAGCTGCAGGGG 
               
               
                   
                   
                 QGLSTATKDTYDALH 
                   
                 GGGCCGTCCACACAAGGGGACTCGACT 
               
               
                   
                   
                 MQALPPR 
                   
                 TTGCGAGTGATAAGCCCACCACCACCC 
               
               
                   
                   
                   
                   
                 CTGCCCCTAGACCTCCAACCCCAGCCC 
               
               
                   
                   
                   
                   
                 CTACAATCGCCAGCCAGCCCCTGAGCC 
               
               
                   
                   
                   
                   
                 TGAGGCCCGAAGCCTGTAGACCTGCCG 
               
               
                   
                   
                   
                   
                 CTGGCGGAGCCGTGCACACCAGAGGCC 
               
               
                   
                   
                   
                   
                 TGGATTTCGCCTGCGACATCTACATCT 
               
               
                   
                   
                   
                   
                 GGGCCCCTCTGGCCGGCACCTGTGGCG 
               
               
                   
                   
                   
                   
                 TGCTGCTGCTGAGCCTGGTCATCACCC 
               
               
                   
                   
                   
                   
                 TGTACTGCAACCACCGGAATAGGAGCA 
               
               
                   
                   
                   
                   
                 AGCGGAGCAGAGGCGGCCACAGCGAC 
               
               
                   
                   
                   
                   
                 TACATGAACATGACCCCCCGGAGGCCT 
               
               
                   
                   
                   
                   
                 GGCCCCACCCGGAAGCACTACCAGCCC 
               
               
                   
                   
                   
                   
                 TACGCCCCTCCCAGGGACTTCGCCGCC 
               
               
                   
                   
                   
                   
                 TACCGGAGCCGGGTGAAGTTCAGCCGG 
               
               
                   
                   
                   
                   
                 AGCGCCGACGCCCCTGCCTACCAGCAG 
               
               
                   
                   
                   
                   
                 GGCCAGAACCAGCTGTACAACGAGCTG 
               
               
                   
                   
                   
                   
                 AACCTGGGCCGGAGGGAGGAGTACGA 
               
               
                   
                   
                   
                   
                 CGTGCTGGACAAGCGGAGAGGCCGGG 
               
               
                   
                   
                   
                   
                 ACCCTGAGATGGGCGGCAAGCCCCGG 
               
               
                   
                   
                   
                   
                 AGAAAGAACCCTCAGGAGGGCCTGTAT 
               
               
                   
                   
                   
                   
                 AACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGA 
               
               
                   
                   
                   
                   
                 AGGGCGAGCGGCGGAGGGGCAAGGGC 
               
               
                   
                   
                   
                   
                 CACGACGGCCTGTACCAGGGCCTGAGC 
               
               
                   
                   
                   
                   
                 ACCGCCACCAAGGATACCTACGACGCC 
               
               
                   
                   
                   
                   
                 CTGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 hROR1 
                 80 
                 EVQLVESGGGLVQPG 
                 227 
                 GAAGTGCAACTGGTCGAGTCTGGGGGC 
               
               
                 (VH_5-VL_16).CD8a(3x).CD28z 
                   
                 GSLRLSCAASGFTFSS 
                   
                 GGCCTTGTGCAACCTGGAGGCAGCCTT 
               
               
                   
                   
                 YAMSWVRQAPGKGL 
                   
                 CGACTCAGTTGCGCCGCGTCTGGTTTT 
               
               
                   
                   
                 EWVSSISRGGTTYYP 
                   
                 ACCTTCTCCTCTTACGCGATGAGCTGG 
               
               
                   
                   
                 DSVKGRFTISRDNSK 
                   
                 GTTCGCCAGGCCCCCGGCAAGGGACTT 
               
               
                   
                   
                 NTLYLQMNSLRAEDT 
                   
                 GAGTGGGTTAGTTCGATCTCCCGCGGA 
               
               
                   
                   
                 AVYYCGRYDYDGYY 
                   
                 GGCACCACATATTATCCTGACTCGGTT 
               
               
                   
                   
                 AMDYWGQGTLVTVS 
                   
                 AAGGGACGCTTCACTATCTCTAGGGAC 
               
               
                   
                   
                 SGGGGSGGGGSGGG 
                   
                 AATTCAAAGAACACACTGTATCTCCAA 
               
               
                   
                   
                 GSDIQMTQSPSSLSAS 
                   
                 ATGAACTCCTTGCGGGCCGAGGACACT 
               
               
                   
                   
                 VGDRVTITCKASPDIN 
                   
                 GCTGTGTATTATTGCGGACGATACGAC 
               
               
                   
                   
                 SYLNWYQQKPGKAP 
                   
                 TACGATGGGTATTACGCCATGGATTAC 
               
               
                   
                   
                 KVLIYRANRLVDGVP 
                   
                 TGGGGGCAAGGTACACTGGTCACTGTG 
               
               
                   
                   
                 SRFSGSGSGTDYTLTI 
                   
                 AGTTCGGGGGGCGGCGGAAGTGGTGG 
               
               
                   
                   
                 SSLQPEDFATYYCLQ 
                   
                 AGGGGGAAGTGGTGGAGGAGGAAGCG 
               
               
                   
                   
                 YDEFPYTFGQGTKVEI 
                   
                 ATATTCAGATGACCCAGTCGCCCAGCA 
               
               
                   
                   
                 KKPTTTPAPRPPTPAP 
                   
                 GTCTCTCGGCCTCAGTGGGCGACCGGG 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 TCACTATCACTTGCAAAGCAAGTCCTG 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 ATATAAACTCCTATCTTAATTGGTATCA 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 GCAGAAGCCCGGCAAGGCACCTAAGG 
               
               
                   
                   
                 TIASQPLSLRPEASRP 
                   
                 TTCTGATATATCGCGCAAATCGGCTCG 
               
               
                   
                   
                 AAGGAVHTRGLDFAS 
                   
                 TGGATGGAGTACCCAGCCGATTTTCCG 
               
               
                   
                   
                 DKPTTTPAPRPPTPAP 
                   
                 GCAGCGGCTCAGGCACTGACTACACAC 
               
               
                   
                   
                 TIASQPLSLRPEACRP 
                   
                 TGACAATCAGCAGCTTGCAGCCTGAAG 
               
               
                   
                   
                 AAGGAVHTRGLDFA 
                   
                 ATTTCGCCACATACTATTGTCTACAGTA 
               
               
                   
                   
                 CDIYIWAPLAGTCGV 
                   
                 CGACGAGTTCCCTTATACATTCGGCCA 
               
               
                   
                   
                 LLLSLVITLYCNHRNR 
                   
                 GGGGACCAAGGTCGAGATCAAGAAGC 
               
               
                   
                   
                 SKRSRGGHSDYMNM 
                   
                 CTACCACCACCCCCGCACCTCGTCCTC 
               
               
                   
                   
                 TPRRPGPTRKHYQPY 
                   
                 CAACCCCTGCACCTACGATTGCCAGTC 
               
               
                   
                   
                 APPRDFAAYRSRVKF 
                   
                 AGCCTCTTTCACTGCGGCCTGAGGCCA 
               
               
                   
                   
                 SRSADAPAYQQGQN 
                   
                 GCAGACCAGCTGCCGGCGGTGCCGTCC 
               
               
                   
                   
                 QLYNELNLGRREEYD 
                   
                 ATACAAGAGGACTGGACTTCGCGTCCG 
               
               
                   
                   
                 VLDKRRGRDPEMGG 
                   
                 ATAAACCTACTACCACTCCAGCCCCAA 
               
               
                   
                   
                 KPRRKNPQEGLYNEL 
                   
                 GGCCCCCAACCCCAGCACCGACTATCG 
               
               
                   
                   
                 QKDKMAEAYSEIGM 
                   
                 CATCACAGCCTTTGTCACTGCGTCCTG 
               
               
                   
                   
                 KGERRRGKGHDGLY 
                   
                 AAGCCAGCCGGCCAGCTGCAGGGGGG 
               
               
                   
                   
                 QGLSTATKDTYDALH 
                   
                 GCCGTCCACACAAGGGGACTCGACTTT 
               
               
                   
                   
                 MQALPPR 
                   
                 GCGAGTGATAAGCCCACCACCACCCCT 
               
               
                   
                   
                   
                   
                 GCCCCTAGACCTCCAACCCCAGCCCCT 
               
               
                   
                   
                   
                   
                 ACAATCGCCAGCCAGCCCCTGAGCCTG 
               
               
                   
                   
                   
                   
                 AGGCCCGAAGCCTGTAGACCTGCCGCT 
               
               
                   
                   
                   
                   
                 GGCGGAGCCGTGCACACCAGAGGCCT 
               
               
                   
                   
                   
                   
                 GGATTTCGCCTGCGACATCTACATCTG 
               
               
                   
                   
                   
                   
                 GGCCCCTCTGGCCGGCACCTGTGGCGT 
               
               
                   
                   
                   
                   
                 GCTGCTGCTGAGCCTGGTCATCACCCT 
               
               
                   
                   
                   
                   
                 GTACTGCAACCACCGGAATAGGAGCA 
               
               
                   
                   
                   
                   
                 AGCGGAGCAGAGGCGGCCACAGCGAC 
               
               
                   
                   
                   
                   
                 TACATGAACATGACCCCCCGGAGGCCT 
               
               
                   
                   
                   
                   
                 GGCCCCACCCGGAAGCACTACCAGCCC 
               
               
                   
                   
                   
                   
                 TACGCCCCTCCCAGGGACTTCGCCGCC 
               
               
                   
                   
                   
                   
                 TACCGGAGCCGGGTGAAGTTCAGCCGG 
               
               
                   
                   
                   
                   
                 AGCGCCGACGCCCCTGCCTACCAGCAG 
               
               
                   
                   
                   
                   
                 GGCCAGAACCAGCTGTACAACGAGCTG 
               
               
                   
                   
                   
                   
                 AACCTGGGCCGGAGGGAGGAGTACGA 
               
               
                   
                   
                   
                   
                 CGTGCTGGACAAGCGGAGAGGCCGGG 
               
               
                   
                   
                   
                   
                 ACCCTGAGATGGGCGGCAAGCCCCGG 
               
               
                   
                   
                   
                   
                 AGAAAGAACCCTCAGGAGGGCCTGTAT 
               
               
                   
                   
                   
                   
                 AACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGA 
               
               
                   
                   
                   
                   
                 AGGGCGAGCGGCGGAGGGGCAAGGGC 
               
               
                   
                   
                   
                   
                 CACGACGGCCTGTACCAGGGCCTGAGC 
               
               
                   
                   
                   
                   
                 ACCGCCACCAAGGATACCTACGACGCC 
               
               
                   
                   
                   
                   
                 CTGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 hROR1 
                 81 
                 EVQLVESGGGLVQPG 
                 228 
                 GAGGTTCAACTCGTGGAGTCTGGAGGC 
               
               
                 (VH_18-VL_04).CD8a(3x).CD28z 
                   
                 GSLRLSCSASGFTFSS 
                   
                 GGGCTAGTGCAGCCTGGCGGCTCCCTG 
               
               
                   
                   
                 YAMSWVRQVPGKGL 
                   
                 CGACTGTCTTGCAGCGCATCAGGCTTT 
               
               
                   
                   
                 VWISSISRGGTTYYAD 
                   
                 ACATTCAGTTCTTATGCCATGAGCTGG 
               
               
                   
                   
                 SVRGRFIISRDNAKNT 
                   
                 GTGAGGCAGGTGCCCGGCAAGGGTCTG 
               
               
                   
                   
                 LYLEMNNLRGEDTA 
                   
                 GTGTGGATCAGCTCAATCTCCAGGGGC 
               
               
                   
                   
                 VYYCARYDYDGYYA 
                   
                 GGGACTACATATTACGCCGATTCGGTC 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AGGGGTCGTTTTATCATTAGCAGGGAT 
               
               
                   
                   
                 GGGGSGGGGSGGGG 
                   
                 AATGCCAAGAACACCTTGTATTTGGAG 
               
               
                   
                   
                 SDIQMTQSPSSLSASV 
                   
                 ATGAACAACCTAAGAGGCGAAGACAC 
               
               
                   
                   
                 GDRVTITCQASPDINS 
                   
                 CGCTGTGTACTATTGTGCCCGTTACGA 
               
               
                   
                   
                 YLNWYQQKPGKAPK 
                   
                 CTACGATGGGTACTACGCCATGGACTA 
               
               
                   
                   
                 LLIYRANNLETGVPSR 
                   
                 TTGGGGCCAGGGAACCTTGGTGACTGT 
               
               
                   
                   
                 FSGSGSGTDFTLTISSL 
                   
                 GTCAAGTGGCGGGGGCGGCAGCGGAG 
               
               
                   
                   
                 QPEDIATYYCLQYDE 
                   
                 GCGGTGGCAGCGGAGGCGGCGGTTCTG 
               
               
                   
                   
                 FPYTFGQGTKLEIKKP 
                   
                 ATATTCAAATGACGCAAAGTCCCAGCA 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 GCCTCTCCGCCTCCGTTGGAGACAGGG 
               
               
                   
                   
                 QPLSLRPEASRPAAG 
                   
                 TGACTATTACATGCCAAGCCAGCCCCG 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 ATATTAATAGCTACTTAAATTGGTATC 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 AGCAGAAACCTGGGAAGGCACCTAAA 
               
               
                   
                   
                 QPLSLRPEASRPAAG 
                   
                 CTTCTCATCTACCGCGCTAACAATCTG 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 GAGACCGGCGTGCCGTCTAGATTTTCC 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 GGCTCTGGATCAGGGACCGATTTTACT 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 CTGACAATTAGTTCCCTGCAACCCGAA 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 GACATCGCCACTTATTATTGCCTGCAA 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 TATGATGAGTTTCCTTACACATTTGGTC 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 AGGGAACTAAACTAGAGATTAAGAAG 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 CCTACCACCACCCCCGCACCTCGTCCT 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 CCAACCCCTGCACCTACGATTGCCAGT 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 CAGCCTCTTTCACTGCGGCCTGAGGCC 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 AGCAGACCAGCTGCCGGCGGTGCCGTC 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 CATACAAGAGGACTGGACTTCGCGTCC 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 GATAAACCTACTACCACTCCAGCCCCA 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 AGGCCCCCAACCCCAGCACCGACTATC 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 GCATCACAGCCTTTGTCACTGCGTCCT 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 GAAGCCAGCCGGCCAGCTGCAGGGGG 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 GGCCGTCCACACAAGGGGACTCGACTT 
               
               
                   
                   
                 PPR 
                   
                 TGCGAGTGATAAGCCCACCACCACCCC 
               
               
                   
                   
                   
                   
                 TGCCCCTAGACCTCCAACCCCAGCCCC 
               
               
                   
                   
                   
                   
                 TACAATCGCCAGCCAGCCCCTGAGCCT 
               
               
                   
                   
                   
                   
                 GAGGCCCGAAGCCTGTAGACCTGCCGC 
               
               
                   
                   
                   
                   
                 TGGCGGAGCCGTGCACACCAGAGGCCT 
               
               
                   
                   
                   
                   
                 GGATTTCGCCTGCGACATCTACATCTG 
               
               
                   
                   
                   
                   
                 GGCCCCTCTGGCCGGCACCTGTGGCGT 
               
               
                   
                   
                   
                   
                 GCTGCTGCTGAGCCTGGTCATCACCCT 
               
               
                   
                   
                   
                   
                 GTACTGCAACCACCGGAATAGGAGCA 
               
               
                   
                   
                   
                   
                 AGCGGAGCAGAGGCGGCCACAGCGAC 
               
               
                   
                   
                   
                   
                 TACATGAACATGACCCCCCGGAGGCCT 
               
               
                   
                   
                   
                   
                 GGCCCCACCCGGAAGCACTACCAGCCC 
               
               
                   
                   
                   
                   
                 TACGCCCCTCCCAGGGACTTCGCCGCC 
               
               
                   
                   
                   
                   
                 TACCGGAGCCGGGTGAAGTTCAGCCGG 
               
               
                   
                   
                   
                   
                 AGCGCCGACGCCCCTGCCTACCAGCAG 
               
               
                   
                   
                   
                   
                 GGCCAGAACCAGCTGTACAACGAGCTG 
               
               
                   
                   
                   
                   
                 AACCTGGGCCGGAGGGAGGAGTACGA 
               
               
                   
                   
                   
                   
                 CGTGCTGGACAAGCGGAGAGGCCGGG 
               
               
                   
                   
                   
                   
                 ACCCTGAGATGGGCGGCAAGCCCCGG 
               
               
                   
                   
                   
                   
                 AGAAAGAACCCTCAGGAGGGCCTGTAT 
               
               
                   
                   
                   
                   
                 AACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGA 
               
               
                   
                   
                   
                   
                 AGGGCGAGCGGCGGAGGGGCAAGGGC 
               
               
                   
                   
                   
                   
                 CACGACGGCCTGTACCAGGGCCTGAGC 
               
               
                   
                   
                   
                   
                 ACCGCCACCAAGGATACCTACGACGCC 
               
               
                   
                   
                   
                   
                 CTGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 hROR1 
                 82 
                 EVQLVESGGGLVQPG 
                 229 
                 GAGGTTCAACTCGTGGAGTCTGGAGGC 
               
               
                 (VH_18-VL_14).CD8a(3x).CD28z 
                   
                 GSLRLSCSASGFTFSS 
                   
                 GGGCTAGTGCAGCCTGGCGGCTCCCTG 
               
               
                   
                   
                 YAMSWVRQVPGKGL 
                   
                 CGACTGTCTTGCAGCGCATCAGGCTTT 
               
               
                   
                   
                 VWISSISRGGTTYYAD 
                   
                 ACATTCAGTTCTTATGCCATGAGCTGG 
               
               
                   
                   
                 SVRGRFIISRDNAKNT 
                   
                 GTGAGGCAGGTGCCCGGCAAGGGTCTG 
               
               
                   
                   
                 LYLEMNNLRGEDTA 
                   
                 GTGTGGATCAGCTCAATCTCCAGGGGC 
               
               
                   
                   
                 VYYCARYDYDGYYA 
                   
                 GGGACTACATATTACGCCGATTCGGTC 
               
               
                   
                   
                 MDYWGQGTLVTVSS 
                   
                 AGGGGTCGTTTTATCATTAGCAGGGAT 
               
               
                   
                   
                 GGGGSGGGGSGGGG 
                   
                 AATGCCAAGAACACCTTGTATTTGGAG 
               
               
                   
                   
                 SDIQMTQSPSSLSASV 
                   
                 ATGAACAACCTAAGAGGCGAAGACAC 
               
               
                   
                   
                 GDRVTITCKASPDINS 
                   
                 CGCTGTGTACTATTGTGCCCGTTACGA 
               
               
                   
                   
                 YLNWYQQKPGKAPK 
                   
                 CTACGATGGGTACTACGCCATGGACTA 
               
               
                   
                   
                 LLIYRANRLVDGVPS 
                   
                 TTGGGGCCAGGGAACCTTGGTGACTGT 
               
               
                   
                   
                 RFSGSGSGTDYTLTIS 
                   
                 GTCAAGTGGCGGGGGCGGCAGCGGAG 
               
               
                   
                   
                 SLQPEDFATYYCLQY 
                   
                 GCGGTGGCAGCGGAGGCGGCGGTTCTG 
               
               
                   
                   
                 DEFPYTFGAGTKVEIK 
                   
                 ATATACAGATGACACAGAGCCCTTCAA 
               
               
                   
                   
                 KPTTTPAPRPPTPAPTI 
                   
                 GTTTATCTGCAAGCGTCGGCGATCGTG 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 TTACAATAACTTGCAAGGCATCTCCCG 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 ACATCAATTCCTACCTCAACTGGTATC 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 AGCAGAAGCCTGGGAAGGCTCCTAAG 
               
               
                   
                   
                 SQPLSLRPEASRPAAG 
                   
                 CTGCTTATTTACAGAGCAAATCGCCTG 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 GTGGACGGCGTGCCCAGTCGGTTTTCC 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 GGGTCTGGGAGCGGAACGGATTACAC 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 ACTGACCATCTCAAGCCTGCAACCCGA 
               
               
                   
                   
                 GAVHTRGLDFACDIY 
                   
                 AGACTTCGCTACATATTACTGCCTTCA 
               
               
                   
                   
                 IWAPLAGTCGVLLLS 
                   
                 GTATGATGAGTTCCCATATACCTTCGG 
               
               
                   
                   
                 LVITLYCNHRNRSKR 
                   
                 CGCTGGGACCAAGGTGGAGATAAAGA 
               
               
                   
                   
                 SRGGHSDYMNMTPR 
                   
                 AGCCTACCACCACCCCCGCACCTCGTC 
               
               
                   
                   
                 RPGPTRKHYQPYAPP 
                   
                 CTCCAACCCCTGCACCTACGATTGCCA 
               
               
                   
                   
                 RDFAAYRSRVKFSRS 
                   
                 GTCAGCCTCTTTCACTGCGGCCTGAGG 
               
               
                   
                   
                 ADAPAYQQGQNQLY 
                   
                 CCAGCAGACCAGCTGCCGGCGGTGCCG 
               
               
                   
                   
                 NELNLGRREEYDVLD 
                   
                 TCCATACAAGAGGACTGGACTTCGCGT 
               
               
                   
                   
                 KRRGRDPEMGGKPR 
                   
                 CCGATAAACCTACTACCACTCCAGCCC 
               
               
                   
                   
                 RKNPQEGLYNELQKD 
                   
                 CAAGGCCCCCAACCCCAGCACCGACTA 
               
               
                   
                   
                 KMAEAYSEIGMKGER 
                   
                 TCGCATCACAGCCTTTGTCACTGCGTCC 
               
               
                   
                   
                 RRGKGHDGLYQGLST 
                   
                 TGAAGCCAGCCGGCCAGCTGCAGGGG 
               
               
                   
                   
                 ATKDTYDALHMQAL 
                   
                 GGGCCGTCCACACAAGGGGACTCGACT 
               
               
                   
                   
                 PPR 
                   
                 TTGCGAGTGATAAGCCCACCACCACCC 
               
               
                   
                   
                   
                   
                 CTGCCCCTAGACCTCCAACCCCAGCCC 
               
               
                   
                   
                   
                   
                 CTACAATCGCCAGCCAGCCCCTGAGCC 
               
               
                   
                   
                   
                   
                 TGAGGCCCGAAGCCTGTAGACCTGCCG 
               
               
                   
                   
                   
                   
                 CTGGCGGAGCCGTGCACACCAGAGGCC 
               
               
                   
                   
                   
                   
                 TGGATTTCGCCTGCGACATCTACATCT 
               
               
                   
                   
                   
                   
                 GGGCCCCTCTGGCCGGCACCTGTGGCG 
               
               
                   
                   
                   
                   
                 TGCTGCTGCTGAGCCTGGTCATCACCC 
               
               
                   
                   
                   
                   
                 TGTACTGCAACCACCGGAATAGGAGCA 
               
               
                   
                   
                   
                   
                 AGCGGAGCAGAGGCGGCCACAGCGAC 
               
               
                   
                   
                   
                   
                 TACATGAACATGACCCCCCGGAGGCCT 
               
               
                   
                   
                   
                   
                 GGCCCCACCCGGAAGCACTACCAGCCC 
               
               
                   
                   
                   
                   
                 TACGCCCCTCCCAGGGACTTCGCCGCC 
               
               
                   
                   
                   
                   
                 TACCGGAGCCGGGTGAAGTTCAGCCGG 
               
               
                   
                   
                   
                   
                 AGCGCCGACGCCCCTGCCTACCAGCAG 
               
               
                   
                   
                   
                   
                 GGCCAGAACCAGCTGTACAACGAGCTG 
               
               
                   
                   
                   
                   
                 AACCTGGGCCGGAGGGAGGAGTACGA 
               
               
                   
                   
                   
                   
                 CGTGCTGGACAAGCGGAGAGGCCGGG 
               
               
                   
                   
                   
                   
                 ACCCTGAGATGGGCGGCAAGCCCCGG 
               
               
                   
                   
                   
                   
                 AGAAAGAACCCTCAGGAGGGCCTGTAT 
               
               
                   
                   
                   
                   
                 AACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGA 
               
               
                   
                   
                   
                   
                 AGGGCGAGCGGCGGAGGGGCAAGGGC 
               
               
                   
                   
                   
                   
                 CACGACGGCCTGTACCAGGGCCTGAGC 
               
               
                   
                   
                   
                   
                 ACCGCCACCAAGGATACCTACGACGCC 
               
               
                   
                   
                   
                   
                 CTGCACATGCAGGCCCTGCCCCCCAGA 
               
               
                   
               
               
                 CD8α 
                 83 
                 KPTTTPAPRPPTPAPTIA 
                 230 
                 AAGCCCACCACCACCCCTGCCCCTAGACCT 
               
               
                 hinge 
                   
                 SQPLSLRPEACRPAAGG 
                   
                 CCAACCCCAGCCCCTACAATCGCCAGCCAG 
               
               
                   
                   
                 AVHTRGLDFACD 
                   
                 CCCCTGAGCCTGAGGCCCGAAGCCTGTAG 
               
               
                   
                   
                   
                   
                 ACCTGCCGCTGGCGGAGCCGTGCACACCA 
               
               
                   
                   
                   
                   
                 GAGGCCTGGATTTCGCCTGCGAC 
               
               
                   
               
               
                 CD8α 2x 
                 84 
                 KPTTTPAPRPPTPAPTI 
                 231 
                 AAACCTACTACAACTCCTGCCCCCCGG 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 CCTCCTACACCAGCTCCTACTATCGCCT 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 CCCAGCCACTCAGTCTCAGACCCGAGG 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 CTTCTAGGCCAGCGGCCGGAGGCGCGG 
               
               
                   
                   
                 SQPLSLRPEACRPAAG 
                   
                 TCCACACCCGCGGGCTGGACTTTGCAT 
               
               
                   
                   
                 GAVHTRGLDFACD 
                   
                 CCGATAAGCCCACCACCACCCCTGCCC 
               
               
                   
                   
                   
                   
                 CTAGACCTCCAACCCCAGCCCCTACAA 
               
               
                   
                   
                   
                   
                 TCGCCAGCCAGCCCCTGAGCCTGAGGC 
               
               
                   
                   
                   
                   
                 CCGAAGCCTGTAGACCTGCCGCTGGCG 
               
               
                   
                   
                   
                   
                 GAGCCGTGCACACCAGAGGCCTGGATT 
               
               
                   
                   
                   
                   
                 TCGCCTGCGAC 
               
               
                   
               
               
                 CD8α 3x 
                 85 
                 KPTTTPAPRPPTPAPTI 
                 232 
                 AAGCCTACCACCACCCCCGCACCTCGT 
               
               
                   
                   
                 ASQPLSLRPEASRPAA 
                   
                 CCTCCAACCCCTGCACCTACGATTGCC 
               
               
                   
                   
                 GGAVHTRGLDFASDK 
                   
                 AGTCAGCCTCTTTCACTGCGGCCTGAG 
               
               
                   
                   
                 PTTTPAPRPPTPAPTIA 
                   
                 GCCAGCAGACCAGCTGCCGGCGGTGCC 
               
               
                   
                   
                 SQPLSLRPEASRPAAG 
                   
                 GTCCATACAAGAGGACTGGACTTCGCG 
               
               
                   
                   
                 GAVHTRGLDFASDKP 
                   
                 TCCGATAAACCTACTACCACTCCAGCC 
               
               
                   
                   
                 TTTPAPRPPTPAPTIAS 
                   
                 CCAAGGCCCCCAACCCCAGCACCGACT 
               
               
                   
                   
                 QPLSLRPEACRPAAG 
                   
                 ATCGCATCACAGCCTTTGTCACTGCGT 
               
               
                   
                   
                 GAVHTRGLDFACD 
                   
                 CCTGAAGCCAGCCGGCCAGCTGCAGGG 
               
               
                   
                   
                   
                   
                 GGGGCCGTCCACACAAGGGGACTCGA 
               
               
                   
                   
                   
                   
                 CTTTGCGAGTGATAAGCCCACCACCAC 
               
               
                   
                   
                   
                   
                 CCCTGCCCCTAGACCTCCAACCCCAGC 
               
               
                   
                   
                   
                   
                 CCCTACAATCGCCAGCCAGCCCCTGAG 
               
               
                   
                   
                   
                   
                 CCTGAGGCCCGAAGCCTGTAGACCTGC 
               
               
                   
                   
                   
                   
                 CGCTGGCGGAGCCGTGCACACCAGAG 
               
               
                   
                   
                   
                   
                 GCCTGGATTTCGCCTGCGAC 
               
               
                   
               
               
                 CD8α 4x 
                 86 
                 TTPAPRPPTPAPTIASQ 
                 233 
                 AAGCCTACCACCACCCCCGCACCTCGT 
               
               
                   
                   
                 PLSLRPEASRPAAGG 
                   
                 CCTCCAACCCCTGCACCTACGATTGCC 
               
               
                   
                   
                 AVHTRGLDFASDKPT 
                   
                 AGTCAGCCTCTTTCACTGCGGCCTGAG 
               
               
                   
                   
                 TTPAPRPPTPAPTIASQ 
                   
                 GCCAGCAGACCAGCTGCCGGCGGTGCC 
               
               
                   
                   
                 PLSLRPEASRPAAGG 
                   
                 GTCCATACAAGAGGACTGGACTTCGCG 
               
               
                   
                   
                 AVHTRGLDFASDKPT 
                   
                 TCCGATAAACCTACTACCACTCCAGCC 
               
               
                   
                   
                 TTPAPRPPTPAPTIASQ 
                   
                 CCAAGGCCCCCAACCCCAGCACCGACT 
               
               
                   
                   
                 PLSLRPEASRPAAGG 
                   
                 ATCGCATCACAGCCTTTGTCACTGCGT 
               
               
                   
                   
                 AVHTRGLDFASDKPT 
                   
                 CCTGAAGCCAGCCGGCCAGCTGCAGGG 
               
               
                   
                   
                 TTPAPRPPTPAPTIASQ 
                   
                 GGGGCCGTCCACACAAGGGGACTCGA 
               
               
                   
                   
                 PLSLRPEACRPAAGG 
                   
                 CTTTGCGAGTGATAAACCTACTACAAC 
               
               
                   
                   
                 AVHTRGLDFACD 
                   
                 TCCTGCCCCCCGGCCTCCTACACCAGC 
               
               
                   
                   
                   
                   
                 TCCTACTATCGCCTCCCAGCCACTCAGT 
               
               
                   
                   
                   
                   
                 CTCAGACCCGAGGCTTCTAGGCCAGCG 
               
               
                   
                   
                   
                   
                 GCCGGAGGCGCGGTCCACACCCGCGG 
               
               
                   
                   
                   
                   
                 GCTGGACTTTGCATCCGATAAGCCCAC 
               
               
                   
                   
                   
                   
                 CACCACCCCTGCCCCTAGACCTCCAAC 
               
               
                   
                   
                   
                   
                 CCCAGCCCCTACAATCGCCAGCCAGCC 
               
               
                   
                   
                   
                   
                 CCTGAGCCTGAGGCCCGAAGCCTGTAG 
               
               
                   
                   
                   
                   
                 ACCTGCCGCTGGCGGAGCCGTGCACAC 
               
               
                   
                   
                   
                   
                 CAGAGGCCTGGATTTCGCCTGCGAC 
               
               
                   
               
               
                 CD8α TM 
                 87 
                 IYIWAPLAGTCGVLLLS 
                 234 
                 ATCTACATCTGGGCCCCTCTGGCCGGCACC 
               
               
                   
                   
                 LVITLYCNHRN 
                   
                 TGTGGCGTGCTGCTGCTGAGCCTGGTCATC 
               
               
                   
                   
                   
                   
                 ACCCTGTACTGCAACCACCGGAAT 
               
               
                   
               
               
                 CD28 TM 
                 88 
                 FWVLVVVGGVLACYSL 
                 235 
                 TTTTGGGTGCTGGTGGTGGTTGGTGGAGTC 
               
               
                   
                   
                 LVTVAFIIFWV 
                   
                 CTGGCTTGCTATAGCTTGCTAGTAACAGTG 
               
               
                   
                   
                   
                   
                 GCCTTTATTATTTTCTGGGTG 
               
               
                   
               
               
                 4-1BB 
                 89 
                 KRGRKKLLYIFKQPFMR 
                 236 
                 AAGAGAGGCCGGAAGAAACTGCTGTACAT 
               
               
                 signaling 
                   
                 PVQTTQEEDGCSCRFPE 
                   
                 CTTCAAGCAGCCCTTCATGCGGCCCGTGCA 
               
               
                 domain 
                   
                 EEEGGCEL 
                   
                 GACCACCCAGGAAGAGGACGGCTGCAGCT 
               
               
                   
                   
                   
                   
                 GCCGGTTCCCCGAGGAAGAGGAAGGCGGC 
               
               
                   
                   
                   
                   
                 TGCGAACTG 
               
               
                   
               
               
                 CD28 
                 90 
                 RSKRSRGGHSDYMNMT 
                 237 
                 AGGAGCAAGCGGAGCAGAGGCGGCCACAG 
               
               
                 signaling 
                   
                 PRRPGPTRKHYQPYAPP 
                   
                 CGACTACATGAACATGACCCCCCGGAGGC 
               
               
                 domain 
                   
                 RDFAAYRS 
                   
                 CTGGCCCCACCCGGAAGCACTACCAGCCCT 
               
               
                   
                   
                   
                   
                 ACGCCCCTCCCAGGGACTTCGCCGCCTACC 
               
               
                   
                   
                   
                   
                 GGAGC 
               
               
                   
               
               
                 DNAX- 
                 91 
                 LCARPRRSPAQEDGK 
                 238 
                 CTGTGCGCACGCCCACGCCGCAGCCCC 
               
               
                 activation 
                   
                 VYINMPGRG 
                   
                 GCCCAAGAAGATGGCAAAGTCTACATC 
               
               
                 protein 10 
                   
                   
                   
                 AACATGCCAGGCAGGGGC 
               
               
                 (DAP10) 
                   
                   
                   
                   
               
               
                 Signaling 
                   
                   
                   
                   
               
               
                 Domain 
                   
                   
                   
                   
               
               
                   
               
               
                 DNAX- 
                 92 
                 YFLGRLVPRGRGAAE 
                 239 
                 TACTTCCTGGGCCGGCTGGTCCCTCGG 
               
               
                 activation 
                   
                 AATRKQRITETESPYQ 
                   
                 GGGCGAGGGGCTGCGGAGGCAGCGAC 
               
               
                 protein 12 
                   
                 ELQGQRSDVYSDLNT 
                   
                 CCGGAAACAGCGTATCACTGAGACCGA 
               
               
                 (DAP12) 
                   
                 QRPYYK 
                   
                 GTCGCCTTATCAGGAGCTCCAGGGTCA 
               
               
                 Signaling 
                   
                   
                   
                 GAGGTCGGATGTCTACAGCGACCTCAA 
               
               
                 Domain 
                   
                   
                   
                 CACACAGAGGCCGTATTACAAA 
               
               
                   
               
               
                 CD3ζ 
                 93 
                 RVKFSRSADAPAYQQG 
                 240 
                 CGGGTGAAGTTCAGCCGGAGCGCCGACGC 
               
               
                 signaling 
                   
                 QNQLYNELNLGRREEY 
                   
                 CCCTGCCTACCAGCAGGGCCAGAACCAGC 
               
               
                 domain 
                   
                 DVLDKRRGRDPEMGGK 
                   
                 TGTACAACGAGCTGAACCTGGGCCGGAGG 
               
               
                   
                   
                 PRRKNPQEGLYNELQK 
                   
                 GAGGAGTACGACGTGCTGGACAAGCGGAG 
               
               
                   
                   
                 DKMAEAYSEIGMKGER 
                   
                 AGGCCGGGACCCTGAGATGGGCGGCAAGC 
               
               
                   
                   
                 RRGKGHDGLYQGLSTA 
                   
                 CCCGGAGAAAGAACCCTCAGGAGGGCCTG 
               
               
                   
                   
                 TKDTYDALHMQALPPR 
                   
                 TATAACGAACTGCAGAAAGACAAGATGGC 
               
               
                   
                   
                   
                   
                 CGAGGCCTACAGCGAGATCGGCATGAAGG 
               
               
                   
                   
                   
                   
                 GCGAGCGGCGGAGGGGCAAGGGCCACGAC 
               
               
                   
                   
                   
                   
                 GGCCTGTACCAGGGCCTGAGCACCGCCAC 
               
               
                   
                   
                   
                   
                 CAAGGATACCTACGACGCCCTGCACATGC 
               
               
                   
                   
                   
                   
                 AGGCCCTGCCCCCCAGA 
               
               
                   
               
            
           
           
               
            
               
                 SIGNAL PEPTIDES 
               
            
           
           
               
               
               
               
               
            
               
                 GMCSF 
                 94 
                 MLLLVTSLLLCELPHP 
                 241 
                 ATGCTTCTCCTGGTGACAAGCCTTCTGC 
               
               
                 R alpha 
                   
                 AFLLIP 
                   
                 TCTGTGAGTTACCACACCCAGCATTCC 
               
               
                   
                   
                   
                   
                 TCCTGATCCCA 
               
               
                   
               
               
                 Ig Kappa 
                 95 
                 MRLPAQLLGLLMLW 
                 242 
                 ATGAGGCTCCCTGCTCAGCTCCTGGGG 
               
               
                   
                   
                 VPGSSG 
                   
                 CTGCTAATGCTCTGGGTCCCAGGATCC 
               
               
                   
                   
                   
                   
                 AGTGGG 
               
               
                   
               
               
                 Immuno- 
                 96 
                 MDWTWILFLVAAAT 
                 243 
                 ATGGATTGGACCTGGATTCTGTTTCTG 
               
               
                 globulin E 
                   
                 RVHS 
                   
                 GTGGCCGCTGCCACAAGAGTGCACAGC 
               
               
                   
               
               
                 CD8α 
                 97 
                 MALPVTALLLPLALL 
                 244 
                 ATGGCGCTGCCCGTGACCGCCTTGCTC 
               
               
                   
                   
                 LHAARP 
                   
                 CTGCCGCTGGCCTTGCTGCTCCACGCC 
               
               
                   
                   
                   
                   
                 GCCAGGCCG 
               
               
                   
               
               
                 TVB2 
                 98 
                 MGTSLLCWMALCLL 
                 245 
                 ATGGGCACCAGCCTCCTCTGCTGGATG 
               
               
                 (T21A) 
                   
                 GADHADA 
                   
                 GCCCTGTGTCTCCTGGGGGCAGATCAC 
               
               
                   
                   
                   
                   
                 GCAGATGCT 
               
               
                   
               
               
                 CD52 
                 99 
                 MKRFLFLLLTISLLVM 
                 246 
                 ATGAAGCGCTTCCTCTTCCTCCTACTCA 
               
               
                   
                   
                 VQIQTGLS 
                   
                 CCATCAGCCTCCTGGTTATGGTACAGA 
               
               
                   
                   
                   
                   
                 TACAAACTGGACTCTCA 
               
               
                   
               
               
                 Low-affinity 
                 100 
                 MGAGATGRAMDGPR 
                 247 
                 ATGGGGGCAGGTGCCACCGGCCGCGCC 
               
               
                 nerve growth 
                   
                 LLLLLLLGVSLGGA 
                   
                 ATGGACGGGCCGCGCCTGCTGCTGTTG 
               
               
                 factor receptor 
                   
                   
                   
                 CTGCTTCTGGGGGTGTCCCTTGGAGGT 
               
               
                 (LNGFR, TNFRSF 16) 
                   
                   
                   
                 GCC 
               
               
                   
               
               
                 Mouse 
                 101 
                 MGWSCIILFLVATAT 
                 248 
                 ATGGGCTGGTCCTGCATCATCCTGTTTC 
               
               
                 Ig VH 
                   
                 GVHS 
                   
                 TGGTGGCTACCGCCACCGGCGTGCACA 
               
               
                 region 3 
                   
                   
                   
                 GC 
               
               
                 signal 
                   
                   
                   
                   
               
               
                 peptide 
                   
                   
                   
                   
               
               
                   
               
               
                 β2M 
                 102 
                 MSRSVALAVLALLSL 
                 249 
                 ATGTCTCGCTCCGTGGCCTTAGCTGTGC 
               
               
                 signal 
                   
                 SGLEA 
                   
                 TCGCGCTACTCTCTCTTTCTGGCCTGGA 
               
               
                 peptide 
                   
                   
                   
                 GGCT 
               
               
                   
               
               
                 Azurocidin 
                 103 
                 MTRLTVLALLAGLLA 
                 250 
                 ATGACCCGGCTGACAGTCCTGGCCCTG 
               
               
                 signal 
                   
                 SSRA 
                   
                 CTGGCTGGTCTGCTGGCGTCCTCGAGG 
               
               
                 peptide 
                   
                   
                   
                 GCC 
               
               
                   
               
               
                 Human 
                 104 
                 MKWVTFISLLFLFSSA 
                 251 
                 ATGAAGTGGGTAACCTTTATTTCCCTTC 
               
               
                 Serum 
                   
                 YS 
                   
                 TTTTTCTCTTTAGCTCGGCTTATTCC 
               
               
                 Albumin 
                   
                   
                   
                   
               
               
                 signal 
                   
                   
                   
                   
               
               
                 peptide 
                   
                   
                   
                   
               
               
                   
               
               
                 A2M 
                 105 
                 MGKNKLLHPSLVLLL 
                 252 
                 ATGGGGAAGAACAAACTCCTTCATCCA 
               
               
                 receptor 
                   
                 LVLLPTDA 
                   
                 AGTCTGGTTCTTCTCCTCTTGGTCCTCC 
               
               
                 associated 
                   
                   
                   
                 TGCCCACAGACGCC 
               
               
                 protein 
                   
                   
                   
                   
               
               
                 signal peptide 
                   
                   
                   
                   
               
               
                   
               
               
                 IGHV3-23 
                 106 
                 MEFGLSWLFLVAILK 
                 253 
                 ATGGAGTTTGGGCTGAGCTGGCTTTTT 
               
               
                 signal 
                   
                 GVQC 
                   
                 CTTGTGGCTATTTTAAAAGGTGTCCAG 
               
               
                 peptide 
                   
                   
                   
                 TGT 
               
               
                   
               
               
                 IGKV1-D33 
                 107 
                 MDMRVPAQLLGLLL 
                 254 
                 ATGGACATGAGGGTCCCTGCTCAGCTC 
               
               
                 (HuL1) 
                   
                 LWLSGARC 
                   
                 CTGGGGCTCCTGCTGCTCTGGCTCTCA 
               
               
                 signal 
                   
                   
                   
                 GGTGCCAGATGT 
               
               
                 peptide 
                   
                   
                   
                   
               
               
                   
               
               
                 IGHV3- 
                 108 
                 MEFGLSWVFLVALFR 
                 255 
                 ATGGAGTTTGGGCTGAGCTGGGTTTTC 
               
               
                 33(L14F) 
                   
                 GVQC 
                   
                 CTCGTTGCTCTTTTTAGAGGTGTCCAGT 
               
               
                 (HuH7) 
                   
                   
                   
                 GT 
               
               
                 signal 
                   
                   
                   
                   
               
               
                 peptide 
                   
                   
                   
                   
               
               
                   
               
            
           
           
               
            
               
                 KILL SWITCH 
               
            
           
           
               
               
               
               
               
            
               
                 HER1t 
                 109 
                 RKVCNGIGIGEFKDSL 
                 256 
                 CGCAAAGTGTGTAACGGAATAGGTATT 
               
               
                   
                   
                 SINATNIKHFKNCTSIS 
                   
                 GGTGAATTTAAAGACTCACTCTCCATA 
               
               
                   
                   
                 GDLHILPVAFRGDSFT 
                   
                 AATGCTACGAATATTAAACACTTCAAA 
               
               
                   
                   
                 HTPPLDPQELDILKTV 
                   
                 AACTGCACCTCCATCAGTGGCGATCTC 
               
               
                   
                   
                 KEITGFLLIQAWPENR 
                   
                 CACATCCTGCCGGTGGCATTTAGGGGT 
               
               
                   
                   
                 TDLHAFENLEIIRGRT 
                   
                 GACTCCTTCACACATACTCCTCCTCTGG 
               
               
                   
                   
                 KQHGQFSLAVVSLNI 
                   
                 ATCCACAGGAACTGGATATTCTGAAAA 
               
               
                   
                   
                 TSLGLRSLKEISDGDV 
                   
                 CCGTAAAGGAAATCACAGGGTTTTTGC 
               
               
                   
                   
                 IISGNKNLCYANTINW 
                   
                 TGATTCAGGCTTGGCCTGAAAACAGGA 
               
               
                   
                   
                 KKLFGTSGQKTKIISN 
                   
                 CGGACCTCCATGCCTTTGAGAACCTAG 
               
               
                   
                   
                 RGENSCKATGQVCH 
                   
                 AAATCATACGCGGCAGGACCAAGCAA 
               
               
                   
                   
                 ALCSPEGCWGPEPRD 
                   
                 CATGGTCAGTTTTCTCTTGCAGTCGTCA 
               
               
                   
                   
                 CVSCRNVSRGRECVD 
                   
                 GCCTGAACATAACATCCTTGGGATTAC 
               
               
                   
                   
                 KCNLLEGEPREFVEN 
                   
                 GCTCCCTCAAGGAGATAAGTGATGGAG 
               
               
                   
                   
                 SECIQCHPECLPQAM 
                   
                 ATGTGATAATTTCAGGAAACAAAAATT 
               
               
                   
                   
                 NITCTGRGPDNCIQCA 
                   
                 TGTGCTATGCAAATACAATAAACTGGA 
               
               
                   
                   
                 HYIDGPHCVKTCPAG 
                   
                 AAAAACTGTTTGGGACCTCCGGTCAGA 
               
               
                   
                   
                 VMGENNTLVWKYAD 
                   
                 AAACCAAAATTATAAGCAACAGAGGT 
               
               
                   
                   
                 AGHVCHLCHPNCTY 
                   
                 GAAAACAGCTGCAAGGCCACAGGCCA 
               
               
                   
                   
                 GCTGPGLEGCPTNGP 
                   
                 GGTCTGCCATGCCTTGTGCTCCCCCGA 
               
               
                   
                   
                 KIPSIATGMVGALLLL 
                   
                 GGGCTGCTGGGGCCCGGAGCCCAGGG 
               
               
                   
                   
                 LVVALGIGLFM 
                   
                 ACTGCGTCTCTTGCCGGAATGTCAGCC 
               
               
                   
                   
                   
                   
                 GAGGCAGGGAATGCGTGGACAAGTGC 
               
               
                   
                   
                   
                   
                 AACCTTCTGGAGGGTGAGCCAAGGGA 
               
               
                   
                   
                   
                   
                 GTTTGTGGAGAACTCTGAGTGCATACA 
               
               
                   
                   
                   
                   
                 GTGCCACCCAGAGTGCCTGCCTCAGGC 
               
               
                   
                   
                   
                   
                 CATGAACATCACCTGCACAGGACGGGG 
               
               
                   
                   
                   
                   
                 ACCAGACAACTGTATCCAGTGTGCCCA 
               
               
                   
                   
                   
                   
                 CTACATTGACGGCCCCCACTGCGTCAA 
               
               
                   
                   
                   
                   
                 GACCTGCCCGGCAGGAGTCATGGGAG 
               
               
                   
                   
                   
                   
                 AAAACAACACCCTGGTCTGGAAGTACG 
               
               
                   
                   
                   
                   
                 CAGACGCCGGCCATGTGTGCCACCTGT 
               
               
                   
                   
                   
                   
                 GCCATCCAAACTGCACCTACGGATGCA 
               
               
                   
                   
                   
                   
                 CTGGGCCAGGTCTTGAAGGCTGTCCAA 
               
               
                   
                   
                   
                   
                 CGAATGGGCCTAAGATCCCGTCCATCG 
               
               
                   
                   
                   
                   
                 CCACTGGGATGGTGGGGGCCCTCCTCT 
               
               
                   
                   
                   
                   
                 TGCTGCTGGTGGTGGCCCTGGGGATCG 
               
               
                   
                   
                   
                   
                 GCCTCTTCATG 
               
               
                   
               
               
                 HER1t-1 
                 110 
                 RKVCNGIGIGEFKDSL 
                 257 
                 CGCAAAGTGTGTAACGGAATAGGTATT 
               
               
                   
                   
                 SINATNIKHFKNCTSIS 
                   
                 GGTGAATTTAAAGACTCACTCTCCATA 
               
               
                   
                   
                 GDLHILPVAFRGDSFT 
                   
                 AATGCTACGAATATTAAACACTTCAAA 
               
               
                   
                   
                 HTPPLDPQELDILKTV 
                   
                 AACTGCACCTCCATCAGTGGCGATCTC 
               
               
                   
                   
                 KEITGFLLIQAWPENR 
                   
                 CACATCCTGCCGGTGGCATTTAGGGGT 
               
               
                   
                   
                 TDLHAFENLEIIRGRT 
                   
                 GACTCCTTCACACATACTCCTCCTCTGG 
               
               
                   
                   
                 KQHGQFSLAVVSLNI 
                   
                 ATCCACAGGAACTGGATATTCTGAAAA 
               
               
                   
                   
                 TSLGLRSLKEISDGDV 
                   
                 CCGTAAAGGAAATCACAGGGTTTTTGC 
               
               
                   
                   
                 IISGNKNLCYANTINW 
                   
                 TGATTCAGGCTTGGCCTGAAAACAGGA 
               
               
                   
                   
                 KKLFGTSGQKTKIISN 
                   
                 CGGACCTCCATGCCTTTGAGAACCTAG 
               
               
                   
                   
                 RGENSCKATGQVCH 
                   
                 AAATCATACGCGGCAGGACCAAGCAA 
               
               
                   
                   
                 ALCSPEGCWGPEPRD 
                   
                 CATGGTCAGTTTTCTCTTGCAGTCGTCA 
               
               
                   
                   
                 CVSGGGGSGGGSGG 
                   
                 GCCTGAACATAACATCCTTGGGATTAC 
               
               
                   
                   
                 GGSGGGGSFWVLVV 
                   
                 GCTCCCTCAAGGAGATAAGTGATGGAG 
               
               
                   
                   
                 VGGVLACYSLLVTVA 
                   
                 ATGTGATAATTTCAGGAAACAAAAATT 
               
               
                   
                   
                 FIIFWVRSKRS 
                   
                 TGTGCTATGCAAATACAATAAACTGGA 
               
               
                   
                   
                   
                   
                 AAAAACTGTTTGGGACCTCCGGTCAGA 
               
               
                   
                   
                   
                   
                 AAACCAAAATTATAAGCAACAGAGGT 
               
               
                   
                   
                   
                   
                 GAAAACAGCTGCAAGGCCACAGGCCA 
               
               
                   
                   
                   
                   
                 GGTCTGCCATGCCTTGTGCTCCCCCGA 
               
               
                   
                   
                   
                   
                 GGGCTGCTGGGGCCCGGAGCCCAGGG 
               
               
                   
                   
                   
                   
                 ACTGCGTCTCTGGTGGCGGTGGCTCGG 
               
               
                   
                   
                   
                   
                 GCGGTGGTGGGTCGGGTGGCGGCGGAT 
               
               
                   
                   
                   
                   
                 CTGGTGGCGGTGGCTCGTTTTGGGTGC 
               
               
                   
                   
                   
                   
                 TGGTGGTGGTTGGTGGAGTCCTGGCTT 
               
               
                   
                   
                   
                   
                 GCTATAGCTTGCTAGTAACAGTGGCCT 
               
               
                   
                   
                   
                   
                 TTATTATTTTCTGGGTGAGGAGTAAGA 
               
               
                   
                   
                   
                   
                 GGAGC 
               
               
                   
               
               
                 FL CD20 
                 111 
                 MTTPRNSVNGTFPAE 
                 258 
                 ATGACAACACCCAGAAATTCAGTAAAT 
               
               
                   
                   
                 PMKGPIAMQSGPKPL 
                   
                 GGGACTTTCCCGGCAGAGCCAATGAAA 
               
               
                   
                   
                 FRRMSSLVGPTQSFF 
                   
                 GGCCCTATTGCTATGCAATCTGGTCCA 
               
               
                   
                   
                 MRESKTLGAVQIMNG 
                   
                 AAACCACTCTTCAGGAGGATGTCTTCA 
               
               
                   
                   
                 LFHIALGGLLMIPAGI 
                   
                 CTGGTGGGCCCCACGCAAAGCTTCTTC 
               
               
                   
                   
                 YAPICVTVWYPLWG 
                   
                 ATGAGGGAATCTAAGACTTTGGGGGCT 
               
               
                   
                   
                 GIMYIISGSLLAATEK 
                   
                 GTCCAGATTATGAATGGGCTCTTCCAC 
               
               
                   
                   
                 NSRKCLVKGKMIMNS 
                   
                 ATTGCCCTGGGGGGTCTTCTGATGATC 
               
               
                   
                   
                 LSLFAAISGMILSIMDI 
                   
                 CCAGCAGGGATCTATGCACCCATCTGT 
               
               
                   
                   
                 LNIKISHFLKMESLNFI 
                   
                 GTGACTGTGTGGTACCCTCTCTGGGGA 
               
               
                   
                   
                 RAHTPYINIYNCEPAN 
                   
                 GGCATTATGTATATTATTTCCGGATCAC 
               
               
                   
                   
                 PSEKNSPSTQYCYSIQ 
                   
                 TCCTGGCAGCAACGGAGAAAAACTCCA 
               
               
                   
                   
                 SLFLGILSVMLIFAFFQ 
                   
                 GGAAGTGTTTGGTCAAAGGAAAAATG 
               
               
                   
                   
                 ELVIAGIVENEWKRT 
                   
                 ATAATGAATTCATTGAGCCTCTTTGCTG 
               
               
                   
                   
                 CSRPKSNIVLLSAEEK 
                   
                 CCATTTCTGGAATGATTCTTTCAATCAT 
               
               
                   
                   
                 KEQTIEIKEEVVGLTE 
                   
                 GGACATACTTAATATTAAAATTTCCCA 
               
               
                   
                   
                 TSSQPKNEEDIEIIPIQE 
                   
                 TTTTTTAAAAATGGAGAGTCTGAATTTT 
               
               
                   
                   
                 EEEEETETNFPEPPQD 
                   
                 ATTAGAGCTCACACACCATATATTAAC 
               
               
                   
                   
                 QESSPIENDSSP 
                   
                 ATATACAACTGTGAACCAGCTAATCCC 
               
               
                   
                   
                   
                   
                 TCTGAGAAAAACTCCCCATCTACCCAA 
               
               
                   
                   
                   
                   
                 TACTGTTACAGCATACAATCTCTGTTCT 
               
               
                   
                   
                   
                   
                 TGGGCATTTTGTCAGTGATGCTGATCTT 
               
               
                   
                   
                   
                   
                 TGCCTTCTTCCAGGAACTTGTAATAGCT 
               
               
                   
                   
                   
                   
                 GGCATCGTTGAGAATGAATGGAAAAG 
               
               
                   
                   
                   
                   
                 AACGTGCTCCAGACCCAAATCTAACAT 
               
               
                   
                   
                   
                   
                 AGTTCTCCTGTCAGCAGAAGAAAAAAA 
               
               
                   
                   
                   
                   
                 AGAACAGACTATTGAAATAAAAGAAG 
               
               
                   
                   
                   
                   
                 AAGTGGTTGGGCTAACTGAAACATCTT 
               
               
                   
                   
                   
                   
                 CCCAACCAAAGAATGAAGAAGACATT 
               
               
                   
                   
                   
                   
                 GAAATTATTCCAATCCAAGAAGAGGAA 
               
               
                   
                   
                   
                   
                 GAAGAAGAAACAGAGACGAACTTTCC 
               
               
                   
                   
                   
                   
                 AGAACCTCCCCAAGATCAGGAATCCTC 
               
               
                   
                   
                   
                   
                 ACCAATAGAAAATGACAGCTCTCCT 
               
               
                   
               
               
                 CD20t-1 
                 112 
                 MTTPRNSVNGTFPAE 
                 259 
                 ATGACCACACCACGGAACTCTGTGAAT 
               
               
                   
                   
                 PMKGPIAMQSGPKPL 
                   
                 GGCACCTTCCCAGCAGAGCCAATGAAG 
               
               
                   
                   
                 FRRMSSLVGPTQSFF 
                   
                 GGACCAATCGCAATGCAGAGCGGACC 
               
               
                   
                   
                 MRESKTLGAVQIMNG 
                   
                 CAAGCCTCTGTTTCGGAGAATGAGCTC 
               
               
                   
                   
                 LFHIALGGLLMIPAGI 
                   
                 CCTGGTGGGCCCAACCCAGTCCTTCTTT 
               
               
                   
                   
                 YAPICVTVWYPLWG 
                   
                 ATGAGAGAGTCTAAGACACTGGGCGCC 
               
               
                   
                   
                 GIMYIISGSLLAATEK 
                   
                 GTGCAGATCATGAACGGACTGTTCCAC 
               
               
                   
                   
                 NSRKCLVKGKMIMNS 
                   
                 ATCGCCCTGGGAGGACTGCTGATGATC 
               
               
                   
                   
                 LSLFAAISGMILSIMDI 
                   
                 CCAGCCGGCATCTACGCCCCTATCTGC 
               
               
                   
                   
                 LNIKISHFLKMESLNFI 
                   
                 GTGACCGTGTGGTACCCTCTGTGGGGC 
               
               
                   
                   
                 RAHTPYINIYNCEPAN 
                   
                 GGCATCATGTATATCATCTCCGGCTCTC 
               
               
                   
                   
                 PSEKNSPSTQYCYSIQ 
                   
                 TGCTGGCCGCCACAGAGAAGAACAGC 
               
               
                   
                   
                 SLFLGILSVMLIFAFFQ 
                   
                 AGGAAGTGTCTGGTGAAGGGCAAGAT 
               
               
                   
                   
                 ELVIAGIVENEWKRT 
                   
                 GATCATGAATAGCCTGTCCCTGTTTGC 
               
               
                   
                   
                 CSRPKSNIVLLSAEEK 
                   
                 CGCCATCTCTGGCATGATCCTGAGCAT 
               
               
                   
                   
                 KEQTIEIKEEVVGLTE 
                   
                 CATGGACATCCTGAACATCAAGATCAG 
               
               
                   
                   
                 TSSQPKNEEDIE 
                   
                 CCACTTCCTGAAGATGGAGAGCCTGAA 
               
               
                   
                   
                   
                   
                 CTTCATCAGAGCCCACACCCCTTACAT 
               
               
                   
                   
                   
                   
                 CAACATCTATAATTGCGAGCCTGCCAA 
               
               
                   
                   
                   
                   
                 CCCATCCGAGAAGAATTCTCCAAGCAC 
               
               
                   
                   
                   
                   
                 ACAGTACTGTTATTCCATCCAGTCTCTG 
               
               
                   
                   
                   
                   
                 TTCCTGGGCATCCTGTCTGTGATGCTGA 
               
               
                   
                   
                   
                   
                 TCTTTGCCTTCTTTCAGGAGCTGGTCAT 
               
               
                   
                   
                   
                   
                 CGCCGGCATCGTGGAGAACGAGTGGA 
               
               
                   
                   
                   
                   
                 AGAGGACCTGCAGCCGCCCCAAGTCCA 
               
               
                   
                   
                   
                   
                 ATATCGTGCTGCTGTCCGCCGAGGAGA 
               
               
                   
                   
                   
                   
                 AGAAGGAGCAGACAATCGAGATCAAG 
               
               
                   
                   
                   
                   
                 GAGGAGGTGGTGGGCCTGACCGAGAC 
               
               
                   
                   
                   
                   
                 ATCTAGCCAGCCTAAGAATGAGGAGG 
               
               
                   
                   
                   
                   
                 ATATCGAG 
               
               
                   
               
            
           
           
               
            
               
                 mbIL-15 
               
            
           
           
               
               
               
               
               
            
               
                 mbIL15 
                 113 
                 MDWTWILFLVAAAT 
                 260 
                 ATGGATTGGACCTGGATTCTGTTTCTG 
               
               
                   
                   
                 RVHSNWVNVISDLKK 
                   
                 GTGGCCGCTGCCACAAGAGTGCACAGC 
               
               
                   
                   
                 IEDLIQSMHIDATLYT 
                   
                 AACTGGGTGAATGTGATCAGCGACCTG 
               
               
                   
                   
                 ESDVHPSCKVTAMKC 
                   
                 AAGAAGATCGAGGATCTGATCCAGAG 
               
               
                   
                   
                 FLLELQVISLESGDASI 
                   
                 CATGCACATTGATGCCACCCTGTACAC 
               
               
                   
                   
                 HDTVENLIILANNSLS 
                   
                 AGAATCTGATGTGCACCCTAGCTGTAA 
               
               
                   
                   
                 SNGNVTESGCKECEE 
                   
                 AGTGACCGCCATGAAGTGTTTTCTGCT 
               
               
                   
                   
                 LEEKNIKEFLQSFVHI 
                   
                 GGAGCTGCAGGTGATTTCTCTGGAAAG 
               
               
                   
                   
                 VQMFINTSSGGGSGG 
                   
                 CGGAGATGCCTCTATCCACGACACAGT 
               
               
                   
                   
                 GGSGGGGSGGGGSG 
                   
                 GGAGAATCTGATCATCCTGGCCAACAA 
               
               
                   
                   
                 GGSLQITCPPPMSVEH 
                   
                 TAGCCTGAGCAGCAATGGCAATGTGAC 
               
               
                   
                   
                 ADIWVKSYSLYSRER 
                   
                 AGAGTCTGGCTGTAAGGAGTGTGAGGA 
               
               
                   
                   
                 YICNSGFKRKAGTSSL 
                   
                 GCTGGAGGAGAAGAACATCAAGGAGT 
               
               
                   
                   
                 TECVLNKATNVAHW 
                   
                 TTCTGCAGAGCTTTGTGCACATCGTGC 
               
               
                   
                   
                 TTPSLKCIRDPALVHQ 
                   
                 AGATGTTCATCAATACAAGCTCTGGCG 
               
               
                   
                   
                 RPAPPSTVTTAGVTPQ 
                   
                 GAGGATCTGGAGGAGGCGGATCTGGA 
               
               
                   
                   
                 PESLSPSGKEPAASSP 
                   
                 GGAGGAGGCAGTGGAGGCGGAGGATC 
               
               
                   
                   
                 SSNNTAATTAAIVPGS 
                   
                 TGGCGGAGGATCTCTGCAGATTACATG 
               
               
                   
                   
                 QLMPSKSPSTGTTEIS 
                   
                 CCCTCCTCCAATGTCTGTGGAGCACGC 
               
               
                   
                   
                 SHESSHGTPSQTTAK 
                   
                 CGATATTTGGGTGAAGTCCTACAGCCT 
               
               
                   
                   
                 NWELTASASHQPPGV 
                   
                 GTACAGCAGAGAGAGATACATCTGCA 
               
               
                   
                   
                 YPQGHSDTTVAISTST 
                   
                 ACAGCGGCTTTAAGAGAAAGGCCGGC 
               
               
                   
                   
                 VLLCGLSAVSLLACY 
                   
                 ACCTCTTCTCTGACAGAGTGCGTGCTG 
               
               
                   
                   
                 LKSRQTPPLASVEME 
                   
                 AATAAGGCCACAAATGTGGCCCACTGG 
               
               
                   
                   
                 AMEALPVTWGTSSRD 
                   
                 ACAACACCTAGCCTGAAGTGCATTAGA 
               
               
                   
                   
                 EDLENCSHHL 
                   
                 GATCCTGCCCTGGTCCACCAGAGGCCT 
               
               
                   
                   
                   
                   
                 GCCCCTCCATCTACAGTGACAACAGCC 
               
               
                   
                   
                   
                   
                 GGAGTGACACCTCAGCCTGAATCTCTG 
               
               
                   
                   
                   
                   
                 AGCCCTTCTGGAAAAGAACCTGCCGCC 
               
               
                   
                   
                   
                   
                 AGCTCTCCTAGCTCTAATAATACCGCC 
               
               
                   
                   
                   
                   
                 GCCACAACAGCCGCCATTGTGCCTGGA 
               
               
                   
                   
                   
                   
                 TCTCAGCTGATGCCTAGCAAGTCTCCT 
               
               
                   
                   
                   
                   
                 AGCACAGGCACAACAGAGATCAGCAG 
               
               
                   
                   
                   
                   
                 CCACGAATCTTCTCACGGAACACCTTC 
               
               
                   
                   
                   
                   
                 TCAGACCACCGCCAAGAATTGGGAGCT 
               
               
                   
                   
                   
                   
                 GACAGCCTCTGCCTCTCACCAGCCTCC 
               
               
                   
                   
                   
                   
                 AGGAGTGTATCCTCAGGGCCACTCTGA 
               
               
                   
                   
                   
                   
                 TACAACAGTGGCCATCAGCACATCTAC 
               
               
                   
                   
                   
                   
                 AGTGCTGCTGTGTGGACTGTCTGCCGT 
               
               
                   
                   
                   
                   
                 GTCTCTGCTGGCCTGTTACCTGAAGTCT 
               
               
                   
                   
                   
                   
                 AGACAGACACCTCCTCTGGCCTCTGTG 
               
               
                   
                   
                   
                   
                 GAGATGGAGGCCATGGAAGCCCTGCCT 
               
               
                   
                   
                   
                   
                 GTGACATGGGGAACAAGCAGCAGAGA 
               
               
                   
                   
                   
                   
                 TGAGGACCTGGAGAATTGTTCTCACCA 
               
               
                   
                   
                   
                   
                 CCTG 
               
               
                   
               
               
                 IL-15 
                 114 
                 NWVNVISDLKKIEDLI 
                 261 
                 AACTGGGTGAATGTGATCAGCGACCTG 
               
               
                   
                   
                 QSMHIDATLYTESDV 
                   
                 AAGAAGATCGAGGATCTGATCCAGAG 
               
               
                   
                   
                 HPSCKVTAMKCFLLE 
                   
                 CATGCACATTGATGCCACCCTGTACAC 
               
               
                   
                   
                 LQVISLESGDASIHDT 
                   
                 AGAATCTGATGTGCACCCTAGCTGTAA 
               
               
                   
                   
                 VENLIILANNSLSSNG 
                   
                 AGTGACCGCCATGAAGTGTTTTCTGCT 
               
               
                   
                   
                 NVTESGCKECEELEE 
                   
                 GGAGCTGCAGGTGATTTCTCTGGAAAG 
               
               
                   
                   
                 KNIKEFLQSFVHIVQM 
                   
                 CGGAGATGCCTCTATCCACGACACAGT 
               
               
                   
                   
                 FINTS 
                   
                 GGAGAATCTGATCATCCTGGCCAACAA 
               
               
                   
                   
                   
                   
                 TAGCCTGAGCAGCAATGGCAATGTGAC 
               
               
                   
                   
                   
                   
                 AGAGTCTGGCTGTAAGGAGTGTGAGGA 
               
               
                   
                   
                   
                   
                 GCTGGAGGAGAAGAACATCAAGGAGT 
               
               
                   
                   
                   
                   
                 TTCTGCAGAGCTTTGTGCACATCGTGC 
               
               
                   
                   
                   
                   
                 AGATGTTCATCAATACAAGC 
               
               
                   
               
               
                 IL-15Rα 
                 115 
                 ITCPPPMSVEHADIWV 
                 262 
                 ATTACATGCCCTCCTCCAATGTCTGTGG 
               
               
                   
                   
                 KSYSLYSRERYICNSG 
                   
                 AGCACGCCGATATTTGGGTGAAGTCCT 
               
               
                   
                   
                 FKRKAGTSSLTECVL 
                   
                 ACAGCCTGTACAGCAGAGAGAGATAC 
               
               
                   
                   
                 NKATNVAHWTTPSL 
                   
                 ATCTGCAACAGCGGCTTTAAGAGAAAG 
               
               
                   
                   
                 KCIRDPALVHQRPAPP 
                   
                 GCCGGCACCTCTTCTCTGACAGAGTGC 
               
               
                   
                   
                 STVTTAGVTPQPESLS 
                   
                 GTGCTGAATAAGGCCACAAATGTGGCC 
               
               
                   
                   
                 PSGKEPAASSPSSNNT 
                   
                 CACTGGACAACACCTAGCCTGAAGTGC 
               
               
                   
                   
                 AATTAAIVPGSQLMP 
                   
                 ATTAGAGATCCTGCCCTGGTCCACCAG 
               
               
                   
                   
                 SKSPSTGTTEISSHESS 
                   
                 AGGCCTGCCCCTCCATCTACAGTGACA 
               
               
                   
                   
                 HGTPSQTTAKNWELT 
                   
                 ACAGCCGGAGTGACACCTCAGCCTGAA 
               
               
                   
                   
                 ASASHQPPGVYPQGH 
                   
                 TCTCTGAGCCCTTCTGGAAAAGAACCT 
               
               
                   
                   
                 SDTTVAISTSTVLLCG 
                   
                 GCCGCCAGCTCTCCTAGCTCTAATAAT 
               
               
                   
                   
                 LSAVSLLACYLKSRQ 
                   
                 ACCGCCGCCACAACAGCCGCCATTGTG 
               
               
                   
                   
                 TPPLASVEMEAMEAL 
                   
                 CCTGGATCTCAGCTGATGCCTAGCAAG 
               
               
                   
                   
                 PVTWGTSSRDEDLEN 
                   
                 TCTCCTAGCACAGGCACAACAGAGATC 
               
               
                   
                   
                 CSHHL 
                   
                 AGCAGCCACGAATCTTCTCACGGAACA 
               
               
                   
                   
                   
                   
                 CCTTCTCAGACCACCGCCAAGAATTGG 
               
               
                   
                   
                   
                   
                 GAGCTGACAGCCTCTGCCTCTCACCAG 
               
               
                   
                   
                   
                   
                 CCTCCAGGAGTGTATCCTCAGGGCCAC 
               
               
                   
                   
                   
                   
                 TCTGATACAACAGTGGCCATCAGCACA 
               
               
                   
                   
                   
                   
                 TCTACAGTGCTGCTGTGTGGACTGTCT 
               
               
                   
                   
                   
                   
                 GCCGTGTCTCTGCTGGCCTGTTACCTGA 
               
               
                   
                   
                   
                   
                 AGTCTAGACAGACACCTCCTCTGGCCT 
               
               
                   
                   
                   
                   
                 CTGTGGAGATGGAGGCCATGGAAGCCC 
               
               
                   
                   
                   
                   
                 TGCCTGTGACATGGGGAACAAGCAGCA 
               
               
                   
                   
                   
                   
                 GAGATGAGGACCTGGAGAATTGTTCTC 
               
               
                   
                   
                   
                   
                 ACCACCTG 
               
               
                   
               
            
           
           
               
            
               
                 LINKERS 
               
            
           
           
               
               
               
               
               
            
               
                 T2A 
                 116 
                 EGRGSLLTCGDVEEN 
                 263 
                 GAGGGCAGAGGAAGTCTTCTAACATGCGG 
               
               
                   
                   
                 PGP 
                   
                 TGACGTGGAGGAGAATCCCGGCCCT 
               
               
                   
               
               
                 Furin- 
                 117 
                 RAKRGSGEGRGSLLT 
                 264 
                 AGAGCTAAGAGGGGAAGCGGAGAGGGCA 
               
               
                 GSG-T2A 
                   
                 CGDVEENPGP 
                   
                 GAGGAAGTCTGCTAACATGCGGTGACGTC 
               
               
                   
                   
                   
                   
                 GAGGAGAATCCTGGACCT 
               
               
                   
               
               
                 Furin-SGSG- 
                 118 
                 RAKRSGSGEGRGSLL 
                 265 
                 AGGGCCAAGAGGAGTGGCAGCGGCGAGGG 
               
               
                 T2A 
                   
                 TCGDVEENPGP 
                   
                 CAGAGGAAGTCTTCTAACATGCGGTGACGT 
               
               
                   
                   
                   
                   
                 GGAGGAGAATCCCGGCCCT 
               
               
                   
               
               
                 Porcine 
                 119 
                 ATNFSLLKQAGDVEE 
                 266 
                 GCAACGAACTTCTCTCTCCTAAAACAGGCT 
               
               
                 tescho- 
                   
                   
                   
                 GGTGATGTGGAGGAGAATCCTGGTCCA 
               
               
                 virus-1 2A 
                   
                   
                   
                 NPGP 
               
               
                 region 
                   
                   
                   
                   
               
               
                 (P2A) 
                   
                   
                   
                   
               
               
                   
               
               
                 GSG-p2a 
                 120 
                 GSGATNFSLLKQAGD 
                 267 
                 GGAAGCGGAGCTACTAACTTCAGCCTGCTG 
               
               
                   
                   
                 VEENPGP 
                   
                 AAGCAGGCTGGAGACGTGGAGGAGAACCC 
               
               
                   
                   
                   
                   
                 TGGACCT 
               
               
                   
               
               
                 fp2a 
                 121 
                 RAKRAPVKQGSGAT 
                 268 
                 CGTGCAAAGCGTGCACCGGTGAAACAGGG 
               
               
                   
                   
                 NFSLLKQAGDVEENP 
                   
                 AAGCGGAGCTACTAACTTCAGCCTGCTGAA 
               
               
                   
                   
                 GP 
                   
                 GCAGGCTGGAGACGTGGAGGAGAACCCTG 
               
               
                   
                   
                   
                   
                 GACCT 
               
               
                   
               
               
                 Equine 
                 122 
                 QCTNYALLKLAGDVE 
                 269 
                 CAGTGTACTAATTATGCTCTCTTGAAATTG 
               
               
                 rhinitis A 
                   
                 SNPGP 
                   
                 GCTGGAGATGTTGAGAGCAACCCTGGACC 
               
               
                 virus 2A 
                   
                   
                   
                 T 
               
               
                 region 
                   
                   
                   
                   
               
               
                 (E2A) 
                   
                   
                   
                   
               
               
                   
               
               
                 Foot-and- 
                 123 
                 VKQTLNFDLLKLAGD 
                 270 
                 GTCAAACAGACCCTAAACTTTGATCTGCTA 
               
               
                 mouth 
                   
                 VESNPGP 
                   
                 AAACTGGCCGGGGATGTGGAAAGTAATCC 
               
               
                 disease 
                   
                   
                   
                 CGGCCCC 
               
               
                 virus 2A 
                   
                   
                   
                   
               
               
                 region 
                   
                   
                   
                   
               
               
                 (F2A) 
                   
                   
                   
                   
               
               
                   
               
               
                 Linker 
                 124 
                 APVKQGSG 
                   
                   
               
               
                   
               
               
                 Furinlink1 
                 125 
                 RAKR 
                 271 
                 CGTGCAAAGCGT 
               
               
                   
               
               
                 Fmdv 
                 126 
                 RAKRAPVKQTLNFDL 
                 272 
                 AGAGCCAAGAGGGCACCGGTGAAACAGAC 
               
               
                   
                   
                 LKLAGDVESNPGP 
                   
                 TTTGAATTTTGACCTTCTGAAGTTGGCAGG 
               
               
                   
                   
                   
                   
                 AGACGTTGAGTCCAACCCTGGGCCC 
               
               
                   
               
               
                 (G4S)3 
                 127 
                 GGGGSGGGGSGGGG 
                 273 
                 GGTGGCGGTGGCTCGGGCGGTGGTGGGTC 
               
               
                 Linker 
                   
                 S 
                   
                 GGGTGGCGGCGGATCT 
               
               
                   
               
               
                 Whitlow 
                 128 
                 GSTSGSGKPGSGEGST 
                 274 
                 GGCAGCACCTCCGGCAGCGGCAAGCCTGG 
               
               
                 Linker 
                   
                 KG 
                   
                 CAGCGGCGAGGGCAGCACCAAGGGC 
               
               
                   
               
               
                 GSG 
                 129 
                 GSG 
                 275 
                 GGAAGCGGA 
               
               
                 linker 
                   
                   
                   
                   
               
               
                   
               
               
                 SGSG 
                 130 
                 SGSG 
                 276 
                 AGTGGCAGCGGC 
               
               
                 linker 
                   
                   
                   
                   
               
               
                   
               
            
           
           
               
            
               
                 RTS-COMPONENTS 
               
            
           
           
               
               
               
               
               
            
               
                 VP16 
                 131 
                 GPKKKRKVAPPTDVS 
                 277 
                 GGCCCCAAGAAGAAAAGGAAGGTGGCCCC 
               
               
                 activation 
                   
                 LGDELHLDGEDVAM 
                   
                 CCCCACCGACGTGAGCCTGGGCGACGAGC 
               
               
                 domain 
                   
                 AHADALDDFDLDML 
                   
                 TGCACCTGGACGGCGAGGACGTGGCCATG 
               
               
                   
                   
                 GDGDSPGPGFTPHDS 
                   
                 GCCCACGCCGACGCCCTGGACGACTTCGAC 
               
               
                   
                   
                 APYGALDMADFEFEQ 
                   
                 CTGGACATGCTGGGCGACGGCGACAGCCC 
               
               
                   
                   
                 MFTDALGIDEYGG 
                   
                 CGGCCCCGGCTTCACCCCCCACGACAGCGC 
               
               
                   
                   
                   
                   
                 CCCCTACGGCGCCCTGGACATGGCCGACTT 
               
               
                   
                   
                   
                   
                 CGAGTTCGAGCAGATGTTCACCGACGCCCT 
               
               
                   
                   
                   
                   
                 GGGCATCGACGAGTACGGCGGC 
               
               
                   
               
               
                 Retinoid x 
                 132 
                 EMPVDRILEAELAVE 
                 278 
                 GAGATGCCCGTGGACAGGATTCTGGAGGC 
               
               
                 receptor 
                   
                 QKSDQGVEGPGGTG 
                   
                 CGAACTCGCCGTGGAGCAGAAAAGCGACC 
               
               
                 (RxR) 
                   
                 GSGSSPNDPVTNICQA 
                   
                 AGGGCGTGGAGGGCCCCGGCGGAACCGGC 
               
               
                   
                   
                 ADKQLFTLVEWAKRI 
                   
                 GGCAGCGGCAGCAGCCCCAACGACCCCGT 
               
               
                   
                   
                 PHFSSLPLDDQVILLR 
                   
                 GACCAACATCTGCCAGGCCGCCGACAAGC 
               
               
                   
                   
                 AGWNELLIASFSHRSI 
                   
                 AGCTGTTCACCCTGGTGGAGTGGGCCAAG 
               
               
                   
                   
                 DVRDGILLATGLHVH 
                   
                 AGGATTCCCCACTTCAGCAGCCTGCCCCTG 
               
               
                   
                   
                 RNSAHSAGVGAIFDR 
                   
                 GACGACCAGGTGATCCTGCTGAGGGCCGG 
               
               
                   
                   
                 VLTELVSKMRDMRM 
                   
                 ATGGAACGAGCTGCTGATCGCCAGCTTCAG 
               
               
                   
                   
                 DKTELGCLRAIILFNP 
                   
                 CCACAGGAGCATCGACGTGAGGGACGGCA 
               
               
                   
                   
                 EVRGLKSAQEVELLR 
                   
                 TCCTGCTGGCCACCGGCCTGCACGTCCATA 
               
               
                   
                   
                 EKVYAALEEYTRTTH 
                   
                 GGAACAGCGCCCACAGCGCCGGAGTGGGC 
               
               
                   
                   
                 PDEPGRFAKLLLRLPS 
                   
                 GCCATCTTCGACAGGGTGCTGACCGAGCTG 
               
               
                   
                   
                 LRSIGLKCLEHLFFFR 
                   
                 GTGAGCAAGATGAGGGACATGAGGATGGA 
               
               
                   
                   
                 LIGDVPIDTFLMEMLE 
                   
                 CAAGACCGAGCTGGGCTGCCTGAGGGCCA 
               
               
                   
                   
                 SPSDS 
                   
                 TCATCCTGTTCAACCCCGAGGTGAGGGGCC 
               
               
                   
                   
                   
                   
                 TGAAAAGCGCCCAGGAGGTGGAGCTGCTG 
               
               
                   
                   
                   
                   
                 AGGGAGAAGGTGTACGCCGCCCTGGAGGA 
               
               
                   
                   
                   
                   
                 GTACACCAGGACCACCCACCCCGACGAGC 
               
               
                   
                   
                   
                   
                 CCGGCAGATTCGCCAAGCTGCTGCTGAGGC 
               
               
                   
                   
                   
                   
                 TGCCCAGCCTGAGGAGCATCGGCCTGAAG 
               
               
                   
                   
                   
                   
                 TGCCTGGAGCACCTGTTCTTCTTCAGGCTG 
               
               
                   
                   
                   
                   
                 ATCGGCGACGTGCCCATCGACACCTTCCTG 
               
               
                   
                   
                   
                   
                 ATGGAGATGCTGGAGAGCCCCAGCGACAG 
               
               
                   
                   
                   
                   
                 C 
               
               
                   
               
               
                 VP16- 
                 133 
                 GPKKKRKVAPPTDVS 
                 279 
                 GGCCCCAAGAAGAAAAGGAAGGTGGCCCC 
               
               
                 linker- 
                   
                 LGDELHLDGEDVAM 
                   
                 CCCCACCGACGTGAGCCTGGGCGACGAGC 
               
               
                 RxR 
                   
                 AHADALDDFDLDML 
                   
                 TGCACCTGGACGGCGAGGACGTGGCCATG 
               
               
                   
                   
                 GDGDSPGPGFTPHDS 
                   
                 GCCCACGCCGACGCCCTGGACGACTTCGAC 
               
               
                   
                   
                 APYGALDMADFEFEQ 
                   
                 CTGGACATGCTGGGCGACGGCGACAGCCC 
               
               
                   
                   
                 MFTDALGIDEYGGEF 
                   
                 CGGCCCCGGCTTCACCCCCCACGACAGCGC 
               
               
                   
                   
                 EMPVDRILEAELAVE 
                   
                 CCCCTACGGCGCCCTGGACATGGCCGACTT 
               
               
                   
                   
                 QKSDQGVEGPGGTG 
                   
                 CGAGTTCGAGCAGATGTTCACCGACGCCCT 
               
               
                   
                   
                 GSGSSPNDPVTNICQA 
                   
                 GGGCATCGACGAGTACGGCGGCGAATTCG 
               
               
                   
                   
                 ADKQLFTLVEWAKRI 
                   
                 AGATGCCCGTGGACAGGATTCTGGAGGCC 
               
               
                   
                   
                 PHFSSLPLDDQVILLR 
                   
                 GAACTCGCCGTGGAGCAGAAAAGCGACCA 
               
               
                   
                   
                 AGWNELLIASFSHRSI 
                   
                 GGGCGTGGAGGGCCCCGGCGGAACCGGCG 
               
               
                   
                   
                 DVRDGILLATGLHVH 
                   
                 GCAGCGGCAGCAGCCCCAACGACCCCGTG 
               
               
                   
                   
                 RNSAHSAGVGAIFDR 
                   
                 ACCAACATCTGCCAGGCCGCCGACAAGCA 
               
               
                   
                   
                 VLTELVSKMRDMRM 
                   
                 GCTGTTCACCCTGGTGGAGTGGGCCAAGA 
               
               
                   
                   
                 DKTELGCLRAIILFNP 
                   
                 GGATTCCCCACTTCAGCAGCCTGCCCCTGG 
               
               
                   
                   
                 EVRGLKSAQEVELLR 
                   
                 ACGACCAGGTGATCCTGCTGAGGGCCGGA 
               
               
                   
                   
                 EKVYAALEEYTRTTH 
                   
                 TGGAACGAGCTGCTGATCGCCAGCTTCAGC 
               
               
                   
                   
                 PDEPGRFAKLLLRLPS 
                   
                 CACAGGAGCATCGACGTGAGGGACGGCAT 
               
               
                   
                   
                 LRSIGLKCLEHLFFFR 
                   
                 CCTGCTGGCCACCGGCCTGCACGTCCATAG 
               
               
                   
                   
                 LIGDVPIDTFLMEMLE 
                   
                 GAACAGCGCCCACAGCGCCGGAGTGGGCG 
               
               
                   
                   
                 SPSDS 
                   
                 CCATCTTCGACAGGGTGCTGACCGAGCTGG 
               
               
                   
                   
                   
                   
                 TGAGCAAGATGAGGGACATGAGGATGGAC 
               
               
                   
                   
                   
                   
                 AAGACCGAGCTGGGCTGCCTGAGGGCCAT 
               
               
                   
                   
                   
                   
                 CATCCTGTTCAACCCCGAGGTGAGGGGCCT 
               
               
                   
                   
                   
                   
                 GAAAAGCGCCCAGGAGGTGGAGCTGCTGA 
               
               
                   
                   
                   
                   
                 GGGAGAAGGTGTACGCCGCCCTGGAGGAG 
               
               
                   
                   
                   
                   
                 TACACCAGGACCACCCACCCCGACGAGCC 
               
               
                   
                   
                   
                   
                 CGGCAGATTCGCCAAGCTGCTGCTGAGGCT 
               
               
                   
                   
                   
                   
                 GCCCAGCCTGAGGAGCATCGGCCTGAAGT 
               
               
                   
                   
                   
                   
                 GCCTGGAGCACCTGTTCTTCTTCAGGCTGA 
               
               
                   
                   
                   
                   
                 TCGGCGACGTGCCCATCGACACCTTCCTGA 
               
               
                   
                   
                   
                   
                 TGGAGATGCTGGAGAGCCCCAGCGACAGC 
               
               
                   
               
               
                 GAL4 
                 134 
                 MKLLSSIEQACDICRL 
                 280 
                 ATGAAGCTGCTGAGCAGCATCGAGCAGGC 
               
               
                 DNA 
                   
                 KKLKCSKEKPKCAKC 
                   
                 TTGCGACATCTGCAGGCTGAAGAAGCTGA 
               
               
                 Binding 
                   
                 LKNNWECRYSPKTKR 
                   
                 AGTGCAGCAAGGAGAAGCCCAAGTGCGCC 
               
               
                 Domain 
                   
                 SPLTRAHLTEVESRLE 
                   
                 AAGTGCCTGAAGAACAACTGGGAGTGCAG 
               
               
                   
                   
                 RLEQLFLLIFPREDLD 
                   
                 ATACAGCCCCAAGACCAAGAGGAGCCCCC 
               
               
                   
                   
                 MILKMDSLQDIKALL 
                   
                 TGACCAGGGCCCACCTGACCGAGGTGGAG 
               
               
                   
                   
                 TGLFVQDNVNKDAV 
                   
                 AGCAGGCTGGAGAGGCTGGAGCAGCTGTT 
               
               
                   
                   
                 TDRLASVETDMPLTL 
                   
                 CCTGCTGATCTTCCCCAGGGAGGACCTGGA 
               
               
                   
                   
                 RQHRISATSSSEESSN 
                   
                 CATGATCCTGAAGATGGACAGCCTGCAAG 
               
               
                   
                   
                 KGQRQLTVSPEF 
                   
                 ACATCAAGGCCCTGCTGACCGGCCTGTTCG 
               
               
                   
                   
                   
                   
                 TGCAGGACAACGTGAACAAGGACGCCGTG 
               
               
                   
                   
                   
                   
                 ACCGACAGGCTGGCCAGCGTGGAGACCGA 
               
               
                   
                   
                   
                   
                 CATGCCCCTGACCCTGAGGCAGCACAGGA 
               
               
                   
                   
                   
                   
                 TCAGCGCCACCAGCAGCAGCGAGGAGAGC 
               
               
                   
                   
                   
                   
                 AGCAACAAGGGCCAGAGGCAGCTGACCGT 
               
               
                   
                   
                   
                   
                 GAGCCCCGAGTTT 
               
               
                   
               
               
                 Ecdysone 
                 135 
                 IRPECVVPETQCAMK 
                 281 
                 ATCAGGCCCGAGTGCGTGGTGCCCGAG 
               
               
                 Receptor 
                   
                 RKEKKAQKEKDKLP 
                   
                 ACCCAGTGCGCCATGAAAAGGAAGGA 
               
               
                 Ligand 
                   
                 VSTTTVDDHMPPIMQ 
                   
                 GAAGAAGGCCCAGAAGGAGAAGGACA 
               
               
                 Binding 
                   
                 CEPPPPEAARIHEVVP 
                   
                 AGCTGCCCGTGAGCACCACCACCGTCG 
               
               
                 Domain - 
                   
                 RFLSDKLLVTNRQKN 
                   
                 ATGACCACATGCCCCCCATCATGCAGT 
               
               
                 VY 
                   
                 IPQLTANQQFLIARLI 
                   
                 GCGAGCCCCCCCCCCCCGAGGCCGCCA 
               
               
                 variant 
                   
                 WYQDGYEQPSDEDL 
                   
                 GGATTCACGAGGTCGTGCCCAGGTTCC 
               
               
                 (EcR) 
                   
                 KRITQTWQQADDENE 
                   
                 TGAGCGACAAGCTGCTGGTGACCAACA 
               
               
                   
                   
                 ESDTPFRQITEMTILT 
                   
                 GGCAGAAGAACATCCCCCAGCTGACCG 
               
               
                   
                   
                 VQLIVEFAKGLPGFA 
                   
                 CCAACCAGCAGTTCCTGATCGCCAGGC 
               
               
                   
                   
                 KISQPDQITLLKACSS 
                   
                 TGATCTGGTATCAGGACGGCTACGAGC 
               
               
                   
                   
                 EVMMLRVARRYDAA 
                   
                 AGCCCAGCGACGAGGACCTGAAAAGG 
               
               
                   
                   
                 SDSILFANNQAYTRD 
                   
                 ATCACCCAGACCTGGCAGCAGGCCGAC 
               
               
                   
                   
                 NYRKAGMAEVIEDLL 
                   
                 GACGAGAACGAGGAGAGCGACACCCC 
               
               
                   
                   
                 HFCRCMYSMALDNIH 
                   
                 CTTCAGGCAGATCACCGAGATGACCAT 
               
               
                   
                   
                 YALLTAVVIFSDRPGL 
                   
                 CCTGACCGTGCAGCTGATCGTGGAGTT 
               
               
                   
                   
                 EQPQLVEEIQRYYLN 
                   
                 CGCCAAGGGCCTGCCCGGATTCGCCAA 
               
               
                   
                   
                 TLRIYILNQLSGSARS 
                   
                 GATCAGCCAGCCCGACCAGATCACCCT 
               
               
                   
                   
                 SVIYGKILSILSELRTL 
                   
                 GCTGAAGGCTTGCAGCAGCGAGGTGAT 
               
               
                   
                   
                 GMQNSNMCISLKLKN 
                   
                 GATGCTGAGGGTGGCCAGGAGGTACG 
               
               
                   
                   
                 RKLPPFLEEIWDVAD 
                   
                 ACGCCGCCAGCGACAGCATCCTGTTCG 
               
               
                   
                   
                 MSHTQPPPILESPTNL 
                   
                 CCAACAACCAGGCTTACACCAGGGACA 
               
               
                   
                   
                   
                   
                 ACTACAGGAAGGCTGGCATGGCCGAG 
               
               
                   
                   
                   
                   
                 GTGATCGAGGACCTCCTGCACTTCTGC 
               
               
                   
                   
                   
                   
                 AGATGTATGTACAGCATGGCCCTGGAC 
               
               
                   
                   
                   
                   
                 AACATCCACTACGCCCTGCTGACCGCC 
               
               
                   
                   
                   
                   
                 GTGGTGATCTTCAGCGACAGGCCCGGC 
               
               
                   
                   
                   
                   
                 CTGGAGCAGCCCCAGCTGGTGGAGGA 
               
               
                   
                   
                   
                   
                 GATCCAGAGGTACTACCTGAACACCCT 
               
               
                   
                   
                   
                   
                 GAGGATCTACATCCTGAACCAGCTGAG 
               
               
                   
                   
                   
                   
                 CGGCAGCGCCAGGAGCAGCGTGATCTA 
               
               
                   
                   
                   
                   
                 CGGCAAGATCCTGAGCATCCTGAGCGA 
               
               
                   
                   
                   
                   
                 GCTGAGGACCCTGGGAATGCAGAACA 
               
               
                   
                   
                   
                   
                 GCAATATGTGTATCAGCCTGAAGCTGA 
               
               
                   
                   
                   
                   
                 AGAACAGGAAGCTGCCCCCCTTCCTGG 
               
               
                   
                   
                   
                   
                 AGGAGATTTGGGACGTGGCCGACATGA 
               
               
                   
                   
                   
                   
                 GCCACACCCAGCCCCCCCCCATCCTGG 
               
               
                   
                   
                   
                   
                 AGAGCCCCACCAACCTG 
               
               
                   
               
               
                 Ecdysone 
                 136 
                 RPECVVPETQCAMKR 
                 282 
                 CGGCCTGAGTGCGTAGTACCCGAGACT 
               
               
                 Receptor 
                   
                 KEKKAQKEKDKLPVS 
                   
                 CAGTGCGCCATGAAGCGGAAAGAGAA 
               
               
                 Ligand 
                   
                 TTTVDDHMPPIMQCE 
                   
                 GAAAGCACAGAAGGAGAAGGACAAAC 
               
               
                 Binding 
                   
                 PPPPEAARIHEVVPRF 
                   
                 TGCCTGTCAGCACGACGACGGTGGACG 
               
               
                 Domain - 
                   
                 LSDKLLVTNRQKNIP 
                   
                 ACCACATGCCGCCCATTATGCAGTGTG 
               
               
                 VY 
                   
                 QLTANQQFLIARLIW 
                   
                 AACCTCCACCTCCTGAAGCAGCAAGGA 
               
               
                 variant 
                   
                 YQDGYEQPSDEDLKR 
                   
                 TTCACGAAGTGGTCCCAAGGTTTCTCT 
               
               
                 (EcR) 
                   
                 ITQTWQQADDENEES 
                   
                 CCGACAAGCTGTTGGTGACAAACCGGC 
               
               
                   
                   
                 DTPFRQITEMTILTVQ 
                   
                 AGAAAAACATCCCCCAGTTGACAGCCA 
               
               
                   
                   
                 LIVEFAKGLPGFAKIS 
                   
                 ACCAGCAGTTCCTTATCGCCAGGCTCA 
               
               
                   
                   
                 QPDQITLLKACSSEV 
                   
                 TCTGGTACCAGGACGGGTACGAGCAGC 
               
               
                   
                   
                 MMLRVARRYDAASD 
                   
                 CTTCTGATGAAGATTTGAAGAGGATTA 
               
               
                   
                   
                 SILFANNQAYTRDNY 
                   
                 CGCAGACGTGGCAGCAAGCGGACGAT 
               
               
                   
                   
                 RKAGMAEVIEDLLHF 
                   
                 GAAAACGAAGAGTCGGACACTCCCTTC 
               
               
                   
                   
                 CRCMYSMALDNIHY 
                   
                 CGCCAGATCACAGAGATGACTATCCTC 
               
               
                   
                   
                 ALLTAVVIFSDRPGLE 
                   
                 ACGGTCCAACTTATCGTGGAGTTCGCG 
               
               
                   
                   
                 QPQLVEEIQRYYLNT 
                   
                 AAGGGATTGCCAGGGTTCGCCAAGATC 
               
               
                   
                   
                 LRIYILNQLSGSARSS 
                   
                 TCGCAGCCTGATCAAATTACGCTGCTT 
               
               
                   
                   
                 VIYGKILSILSELRTLG 
                   
                 AAGGCTTGCTCAAGTGAGGTAATGATG 
               
               
                   
                   
                 MQNSNMCISLKLKNR 
                   
                 CTCCGAGTCGCGCGACGATACGATGCG 
               
               
                   
                   
                 KLPPFLEEIWDVADM 
                   
                 GCCTCAGACAGTATTCTGTTCGCGAAC 
               
               
                   
                   
                 SHTQPPPILESPTNL 
                   
                 AACCAAGCGTACACTCGCGACAACTAC 
               
               
                   
                   
                   
                   
                 CGCAAGGCTGGCATGGCCGAGGTCATC 
               
               
                   
                   
                   
                   
                 GAGGATCTACTGCACTTCTGCCGGTGC 
               
               
                   
                   
                   
                   
                 ATGTACTCTATGGCGTTGGACAACATC 
               
               
                   
                   
                   
                   
                 CATTACGCGCTGCTCACGGCTGTCGTC 
               
               
                   
                   
                   
                   
                 ATCTTTTCTGACCGGCCAGGGTTGGAG 
               
               
                   
                   
                   
                   
                 CAGCCGCAACTGGTGGAAGAGATCCA 
               
               
                   
                   
                   
                   
                 GCGGTACTACCTGAATACGCTCCGCAT 
               
               
                   
                   
                   
                   
                 CTATATCCTGAACCAGCTGAGCGGGTC 
               
               
                   
                   
                   
                   
                 GGCGCGTTCGTCCGTCATATACGGCAA 
               
               
                   
                   
                   
                   
                 GATCCTCTCAATCCTCTCTGAGCTACGC 
               
               
                   
                   
                   
                   
                 ACGCTCGGCATGCAAAACTCCAACATG 
               
               
                   
                   
                   
                   
                 TGCATCTCCCTCAAGCTCAAGAACAGA 
               
               
                   
                   
                   
                   
                 AAGCTGCCGCCTTTCCTCGAGGAGATC 
               
               
                   
                   
                   
                   
                 TGGGATGTGGCGGACATGTCGCACACC 
               
               
                   
                   
                   
                   
                 CAACCGCCGCCTATCCTCGAGTCCCCC 
               
               
                   
                   
                   
                   
                 ACGAATCTCTAG 
               
               
                   
               
               
                 GAL4- 
                 137 
                 MKLLSSIEQACDICRL 
                 283 
                 ATGAAGCTACTGTCTTCTATCGAACAA 
               
               
                 Linker- 
                   
                 KKLKCSKEKPKCAKC 
                   
                 GCATGCGATATTTGCCGACTTAAAAAG 
               
               
                 EcR 
                   
                 LKNNWECRYSPKTKR 
                   
                 CTCAAGTGCTCCAAAGAAAAACCGAA 
               
               
                   
                   
                 SPLTRAHLTEVESRLE 
                   
                 GTGCGCCAAGTGTCTGAAGAACAACTG 
               
               
                   
                   
                 RLEQLFLLIFPREDLD 
                   
                 GGAGTGTCGCTACTCTCCCAAAACCAA 
               
               
                   
                   
                 MILKMDSLQDIKALL 
                   
                 AAGGTCTCCGCTGACTAGGGCACATCT 
               
               
                   
                   
                 TGLFVQDNVNKDAV 
                   
                 GACAGAAGTGGAATCAAGGCTAGAAA 
               
               
                   
                   
                 TDRLASVETDMPLTL 
                   
                 GACTGGAACAGCTATTTCTACTGATTTT 
               
               
                   
                   
                 RQHRISATSSSEESSN 
                   
                 TCCTCGAGAAGACCTTGACATGATTTT 
               
               
                   
                   
                 KGQRQLTVSPEFPGIR 
                   
                 GAAAATGGATTCTTTACAGGATATAAA 
               
               
                   
                   
                 PECVVPETQCAMKRK 
                   
                 AGCATTGTTAACAGGATTATTTGTACA 
               
               
                   
                   
                 EKKAQKEKDKLPVST 
                   
                 AGATAATGTGAATAAAGATGCCGTCAC 
               
               
                   
                   
                 TTVDDHMPPIMQCEP 
                   
                 AGATAGATTGGCTTCAGTGGAGACTGA 
               
               
                   
                   
                 PPPEAARIHEVVPRFL 
                   
                 TATGCCTCTAACATTGAGACAGCATAG 
               
               
                   
                   
                 SDKLLVTNRQKNIPQ 
                   
                 AATAAGTGCGACATCATCATCGGAAGA 
               
               
                   
                   
                 LTANQQFLIARLIWY 
                   
                 GAGTAGTAACAAAGGTCAAAGACAGT 
               
               
                   
                   
                 QDGYEQPSDEDLKRI 
                   
                 TGACTGTATCGCCGGAATTCCCGGGGA 
               
               
                   
                   
                 TQTWQQADDENEES 
                   
                 TCCGGCCTGAGTGCGTAGTACCCGAGA 
               
               
                   
                   
                 DTPFRQITEMTILTVQ 
                   
                 CTCAGTGCGCCATGAAGCGGAAAGAG 
               
               
                   
                   
                 LIVEFAKGLPGFAKIS 
                   
                 AAGAAAGCACAGAAGGAGAAGGACAA 
               
               
                   
                   
                 QPDQITLLKACSSEV 
                   
                 ACTGCCTGTCAGCACGACGACGGTGGA 
               
               
                   
                   
                 MMLRVARRYDAASD 
                   
                 CGACCACATGCCGCCCATTATGCAGTG 
               
               
                   
                   
                 SILFANNQAYTRDNY 
                   
                 TGAACCTCCACCTCCTGAAGCAGCAAG 
               
               
                   
                   
                 RKAGMAEVIEDLLHF 
                   
                 GATTCACGAAGTGGTCCCAAGGTTTCT 
               
               
                   
                   
                 CRCMYSMALDNIHY 
                   
                 CTCCGACAAGCTGTTGGTGACAAACCG 
               
               
                   
                   
                 ALLTAVVIFSDRPGLE 
                   
                 GCAGAAAAACATCCCCCAGTTGACAGC 
               
               
                   
                   
                 QPQLVEEIQRYYLNT 
                   
                 CAACCAGCAGTTCCTTATCGCCAGGCT 
               
               
                   
                   
                 LRIYILNQLSGSARSS 
                   
                 CATCTGGTACCAGGACGGGTACGAGCA 
               
               
                   
                   
                 VIYGKILSILSELRTLG 
                   
                 GCCTTCTGATGAAGATTTGAAGAGGAT 
               
               
                   
                   
                 MQNSNMCISLKLKNR 
                   
                 TACGCAGACGTGGCAGCAAGCGGACG 
               
               
                   
                   
                 KLPPFLEEIWDVADM 
                   
                 ATGAAAACGAAGAGTCGGACACTCCCT 
               
               
                   
                   
                 SHTQPPPILESPTNL 
                   
                 TCCGCCAGATCACAGAGATGACTATCC 
               
               
                   
                   
                   
                   
                 TCACGGTCCAACTTATCGTGGAGTTCG 
               
               
                   
                   
                   
                   
                 CGAAGGGATTGCCAGGGTTCGCCAAGA 
               
               
                   
                   
                   
                   
                 TCTCGCAGCCTGATCAAATTACGCTGC 
               
               
                   
                   
                   
                   
                 TTAAGGCTTGCTCAAGTGAGGTAATGA 
               
               
                   
                   
                   
                   
                 TGCTCCGAGTCGCGCGACGATACGATG 
               
               
                   
                   
                   
                   
                 CGGCCTCAGACAGTATTCTGTTCGCGA 
               
               
                   
                   
                   
                   
                 ACAACCAAGCGTACACTCGCGACAACT 
               
               
                   
                   
                   
                   
                 ACCGCAAGGCTGGCATGGCCGAGGTCA 
               
               
                   
                   
                   
                   
                 TCGAGGATCTACTGCACTTCTGCCGGT 
               
               
                   
                   
                   
                   
                 GCATGTACTCTATGGCGTTGGACAACA 
               
               
                   
                   
                   
                   
                 TCCATTACGCGCTGCTCACGGCTGTCG 
               
               
                   
                   
                   
                   
                 TCATCTTTTCTGACCGGCCAGGGTTGG 
               
               
                   
                   
                   
                   
                 AGCAGCCGCAACTGGTGGAAGAGATC 
               
               
                   
                   
                   
                   
                 CAGCGGTACTACCTGAATACGCTCCGC 
               
               
                   
                   
                   
                   
                 ATCTATATCCTGAACCAGCTGAGCGGG 
               
               
                   
                   
                   
                   
                 TCGGCGCGTTCGTCCGTCATATACGGC 
               
               
                   
                   
                   
                   
                 AAGATCCTCTCAATCCTCTCTGAGCTA 
               
               
                   
                   
                   
                   
                 CGCACGCTCGGCATGCAAAACTCCAAC 
               
               
                   
                   
                   
                   
                 ATGTGCATCTCCCTCAAGCTCAAGAAC 
               
               
                   
                   
                   
                   
                 AGAAAGCTGCCGCCTTTCCTCGAGGAG 
               
               
                   
                   
                   
                   
                 ATCTGGGATGTGGCGGACATGTCGCAC 
               
               
                   
                   
                   
                   
                 ACCCAACCGCCGCCTATCCTCGAGTCC 
               
               
                   
                   
                   
                   
                 CCCACGAATCTCTAG 
               
               
                   
               
               
                 GAL4- 
                 138 
                 MKLLSSIEQACDICRL 
                 284 
                 ATGAAGCTGCTGAGCAGCATCGAGCAG 
               
               
                 Linker- 
                   
                 KKLKCSKEKPKCAKC 
                   
                 GCTTGCGACATCTGCAGGCTGAAGAAG 
               
               
                 EcR 
                   
                 LKNNWECRYSPKTKR 
                   
                 CTGAAGTGCAGCAAGGAGAAGCCCAA 
               
               
                   
                   
                 SPLTRAHLTEVESRLE 
                   
                 GTGCGCCAAGTGCCTGAAGAACAACTG 
               
               
                   
                   
                 RLEQLFLLIFPREDLD 
                   
                 GGAGTGCAGATACAGCCCCAAGACCA 
               
               
                   
                   
                 MILKMDSLQDIKALL 
                   
                 AGAGGAGCCCCCTGACCAGGGCCCACC 
               
               
                   
                   
                 TGLFVQDNVNKDAV 
                   
                 TGACCGAGGTGGAGAGCAGGCTGGAG 
               
               
                   
                   
                 TDRLASVETDMPLTL 
                   
                 AGGCTGGAGCAGCTGTTCCTGCTGATC 
               
               
                   
                   
                 RQHRISATSSSEESSN 
                   
                 TTCCCCAGGGAGGACCTGGACATGATC 
               
               
                   
                   
                 KGQRQLTVSPEFPGR 
                   
                 CTGAAGATGGACAGCCTGCAAGACATC 
               
               
                   
                   
                 PECVVPETQCAMKRK 
                   
                 AAGGCCCTGCTGACCGGCCTGTTCGTG 
               
               
                   
                   
                 EKKAQKEKDKLPVST 
                   
                 CAGGACAACGTGAACAAGGACGCCGT 
               
               
                   
                   
                 TTVDDHMPPIMQCEP 
                   
                 GACCGACAGGCTGGCCAGCGTGGAGA 
               
               
                   
                   
                 PPPEAARIHEVVPRFL 
                   
                 CCGACATGCCCCTGACCCTGAGGCAGC 
               
               
                   
                   
                 SDKLLVTNRQKNIPQ 
                   
                 ACAGGATCAGCGCCACCAGCAGCAGC 
               
               
                   
                   
                 LTANQQFLIARLIWY 
                   
                 GAGGAGAGCAGCAACAAGGGCCAGAG 
               
               
                   
                   
                 QDGYEQPSDEDLKRI 
                   
                 GCAGCTGACCGTGAGCCCCGAGTTTCC 
               
               
                   
                   
                 TQTWQQADDENEES 
                   
                 CGGGCGGCCTGAGTGCGTAGTACCCGA 
               
               
                   
                   
                 DTPFRQITEMTILTVQ 
                   
                 GACTCAGTGCGCCATGAAGCGGAAAG 
               
               
                   
                   
                 LIVEFAKGLPGFAKIS 
                   
                 AGAAGAAAGCACAGAAGGAGAAGGAC 
               
               
                   
                   
                 QPDQITLLKACSSEV 
                   
                 AAACTGCCTGTCAGCACGACGACGGTG 
               
               
                   
                   
                 MMLRVARRYDAASD 
                   
                 GACGACCACATGCCGCCCATTATGCAG 
               
               
                   
                   
                 SILFANNQAYTRDNY 
                   
                 TGTGAACCTCCACCTCCTGAAGCAGCA 
               
               
                   
                   
                 RKAGMAEVIEDLLHF 
                   
                 AGGATTCACGAAGTGGTCCCAAGGTTT 
               
               
                   
                   
                 CRCMYSMALDNIHY 
                   
                 CTCTCCGACAAGCTGTTGGTGACAAAC 
               
               
                   
                   
                 ALLTAVVIFSDRPGLE 
                   
                 CGGCAGAAAAACATCCCCCAGTTGACA 
               
               
                   
                   
                 QPQLVEEIQRYYLNT 
                   
                 GCCAACCAGCAGTTCCTTATCGCCAGG 
               
               
                   
                   
                 LRIYILNQLSGSARSS 
                   
                 CTCATCTGGTACCAGGACGGGTACGAG 
               
               
                   
                   
                 VIYGKILSILSELRTLG 
                   
                 CAGCCTTCTGATGAAGATTTGAAGAGG 
               
               
                   
                   
                 MQNSNMCISLKLKNR 
                   
                 ATTACGCAGACGTGGCAGCAAGCGGA 
               
               
                   
                   
                 KLPPFLEEIWDVADM 
                   
                 CGATGAAAACGAAGAGTCGGACACTC 
               
               
                   
                   
                 SHTQPPPILESPTNL 
                   
                 CCTTCCGCCAGATCACAGAGATGACTA 
               
               
                   
                   
                   
                   
                 TCCTCACGGTCCAACTTATCGTGGAGT 
               
               
                   
                   
                   
                   
                 TCGCGAAGGGATTGCCAGGGTTCGCCA 
               
               
                   
                   
                   
                   
                 AGATCTCGCAGCCTGATCAAATTACGC 
               
               
                   
                   
                   
                   
                 TGCTTAAGGCTTGCTCAAGTGAGGTAA 
               
               
                   
                   
                   
                   
                 TGATGCTCCGAGTCGCGCGACGATACG 
               
               
                   
                   
                   
                   
                 ATGCGGCCTCAGACAGTATTCTGTTCG 
               
               
                   
                   
                   
                   
                 CGAACAACCAAGCGTACACTCGCGACA 
               
               
                   
                   
                   
                   
                 ACTACCGCAAGGCTGGCATGGCCGAGG 
               
               
                   
                   
                   
                   
                 TCATCGAGGATCTACTGCACTTCTGCC 
               
               
                   
                   
                   
                   
                 GGTGCATGTACTCTATGGCGTTGGACA 
               
               
                   
                   
                   
                   
                 ACATCCATTACGCGCTGCTCACGGCTG 
               
               
                   
                   
                   
                   
                 TCGTCATCTTTTCTGACCGGCCAGGGTT 
               
               
                   
                   
                   
                   
                 GGAGCAGCCGCAACTGGTGGAAGAGA 
               
               
                   
                   
                   
                   
                 TCCAGCGGTACTACCTGAATACGCTCC 
               
               
                   
                   
                   
                   
                 GCATCTATATCCTGAACCAGCTGAGCG 
               
               
                   
                   
                   
                   
                 GGTCGGCGCGTTCGTCCGTCATATACG 
               
               
                   
                   
                   
                   
                 GCAAGATCCTCTCAATCCTCTCTGAGC 
               
               
                   
                   
                   
                   
                 TACGCACGCTCGGCATGCAAAACTCCA 
               
               
                   
                   
                   
                   
                 ACATGTGCATCTCCCTCAAGCTCAAGA 
               
               
                   
                   
                   
                   
                 ACAGAAAGCTGCCGCCTTTCCTCGAGG 
               
               
                   
                   
                   
                   
                 AGATCTGGGATGTGGCGGACATGTCGC 
               
               
                   
                   
                   
                   
                 ACACCCAACCGCCGCCTATCCTCGAGT 
               
               
                   
                   
                   
                   
                 CCCCCACGAATCTCTAG 
               
               
                   
               
            
           
           
               
               
               
            
               
                 Name 
                 SEQ ID NO 
                 Nucleotide Sequence 
               
               
                   
               
               
                 Human EEF1A1 
                 139 
                 GAGCGTGCGTGAGGCTCCGGTGCCCGTCAGTGGGCAGAGCGC 
               
               
                 promoter variant 
                   
                 ACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGGTCGG 
               
               
                   
                   
                 CGATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTG 
               
               
                   
                   
                 GGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGT 
               
               
                   
                   
                 GGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTT 
               
               
                   
                   
                 CTTTTTCGCAACGGGTTTGCCGCCAGAACACAG 
               
               
                   
               
               
                 UBC promoter 
                 140 
                 GGCCTCCGCGCCGGGTTTTGGCGCCTCCCGCGGGCGCCCCCCT 
               
               
                   
                   
                 CCTCACGGCGAGCGCTGCCACGTCAGACGAAGGGCGCAGCGA 
               
               
                   
                   
                 GCGTCCTGATCCTTCCGCCCGGACGCTCAGGACAGCGGCCCGC 
               
               
                   
                   
                 TGCTCATAAGACTCGGCCTTAGAACCCCAGTATCAGCAGAAGG 
               
               
                   
                   
                 ACATTTTAGGACGGGACTTGGGTGACTCTAGGGCACTGGTTTT 
               
               
                   
                   
                 CTTTCCAGAGAGCGGAACAGGCGAGGAAAAGTAGTCCCTTCT 
               
               
                   
                   
                 CGGCGATTCTGCGGAGGGATCTCCGTGGGGCGGTGAACGCCG 
               
               
                   
                   
                 ATGATTATATAAGGACGCGCCGGGTGTGGCACAGCTAGTTCCG 
               
               
                   
                   
                 TCGCAGCCGGGATTTGGGTCGCGGTTCTTGTTTGTGGATCGCT 
               
               
                   
                   
                 GTGATCGTCACTTGGTGAGTAGCGGGCTGCTGGGCTGGGTACG 
               
               
                   
                   
                 TGCGCTCGGGGTTGGCGAGTGTGTTTTGTGAAGTTTTTTAGGC 
               
               
                   
                   
                 ACCTTTTGAAATGTAATCATTTGGGTCAATATGTAATTTTCAGT 
               
               
                   
                   
                 GTTAGACTAGTAAATTGTCCGCTAAATTCTGGCCGTTTTTGGCT 
               
               
                   
                   
                 TTTTTGTTAGACG 
               
               
                   
               
               
                 6 site GAL4-inducible 
                 141 
                 ATTGTTCGGAGCAGTGCGGCGCGTTTAGCGGAGTACTGTCCTC 
               
               
                 proximal factor 
                   
                 CGATATTAATCGGGGCAGACTATTCCGGGGTTTACCGGCGCAC 
               
               
                 binding element (PFB) 
                   
                 TCTCGCCCGAACTTCACCGGCGGTCTTTCGTCCGTGCTTTATCG 
               
               
                   
                   
                 GGGCGGATCACTCCGAAC 
               
               
                   
               
               
                 Synthetic minimal promoter 1 
                 142 
                 AGGTCTATATAAGCAGAGCTCGTTTAGTGAACCCTCATTCTGG 
               
               
                 [Inducible Promoter] 
                   
                 AGACGGATCCCGAGCCGAGTGTTTTGACCTCCATAGAA 
               
               
                   
               
               
                 Synthetic 5′ UTR based on 
                 143 
                 CAGCCGCTAAATCCAAGGTAAGGTCAGAAGA 
               
               
                 RPL6 
                   
                   
               
               
                   
               
               
                 SV40e poly A 
                 144 
                 AACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATA 
               
               
                   
                   
                 GCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCT 
               
               
                   
                   
                 AGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTG 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 Bidirectional 
                 145 
                 ATCGATTAATCTAGCGGCCCTAGACGAGCAGACATGATAAGA 
               
               
                 aCA poly A 
                   
                 TACATTGATGAGTTTGGACAAACCACAACTAGAATGCAGTGA 
               
               
                 [bidirectional poly A] 
                   
                 AAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATT 
               
               
                   
                   
                 TGTAACCATTATAAGCTGCAATAAACAAGTTAACAACAACAAT 
               
               
                   
                   
                 TGCATTCATTTTATGTTTCAGGTTCAGGGGGAGATGTGGGAGG 
               
               
                   
                   
                 TTTTTTAAAGCAAGTAAAACCTCTACAAATGTGGTAAAATCCG 
               
               
                   
                   
                 ATAAGCGTACCTAGAGGC 
               
               
                   
               
               
                 2xRbm3 IRES 
                 146 
                 ACTAGTTTTATAATTTCTTCTTCCAGAATTTCTGACATTTTATA 
               
               
                   
                   
                 ATTTCTTCTTCCAGAAGACTCACAACCTC 
               
               
                   
               
               
                 EMCV IRES 
                 147 
                 CCCCCTCTCCCTCCCCCCCCCCTAACGTTACTGGCCGAAGCCG 
               
               
                   
                   
                 CTTGGAATAAGGCCGGTGTGCGTTTGTCTATATGTTATTTTCCA 
               
               
                   
                   
                 CCATATTGCCGTCTTTTGGCAATGTGAGGGCCCGGAAACCTGG 
               
               
                   
                   
                 CCCTGTCTTCTTGACGAGCATTCCTAGGGGTCTTTCCCCTCTCG 
               
               
                   
                   
                 CCAAAGGAATGCAAGGTCTGTTGAATGTCGTGAAGGAAGCAG 
               
               
                   
                   
                 TTCCTCTGGAAGCTTCTTGAAGACAAACAACGTCTGTAGCGAC 
               
               
                   
                   
                 CCTTTGCAGGCAGCGGAACCCCCCACCTGGCGACAGGTGCCTC 
               
               
                   
                   
                 TGCGGCCAAAAGCCACGTGTATAAGATACACCTGCAAAGGCG 
               
               
                   
                   
                 GCACAACCCCAGTGCCACGTTGTGAGTTGGATAGTTGTGGAAA 
               
               
                   
                   
                 GAGTCAAATGGCTCTCCTCAAGCGTATTCAACAAGGGGCTGAA 
               
               
                   
                   
                 GGATGCCCAGAAGGTACCCCATTGTATGGGATCTGATCTGGGG 
               
               
                   
                   
                 CCTCGGTGCACATGCTTTACATGTGTTTAGTCGAGGTTAAAAA 
               
               
                   
                   
                 ACGTCTAGGCCCCCCGAACCACGGGGACGTGGTTTTCCTTTGA 
               
               
                   
                   
                 AAAACACGATC