Patent application EP19382104A (EP), filed 2019-02-14
Publication number: EP3696191A1
Title: CAR T-CELLS FOR THE TREATMENT OF CD1A-POSITIVE CANCER
Abstract: [0001]    Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor T-cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CARTs fratricide. CD1a is exclusively expressed in cortical T-ALLs, a major subset of T-ALL. The expression of CD1a is restricted to cortical thymocytes and neither CD34+ progenitors nor T-cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. The present invention provides CARs comprising a CD1a-targeting moiety which may be transduced or transformed into T cells. The resultant CARTs are suitable for the treatment of cortical T-ALLS.
IPC codes: A61P  35/    00            A I
C07K  14/   725            A I
C07K  16/    28            A I
C12N   5/  0783            A I
Claims: number: 1
text: A chimeric antigen receptor (CAR) comprising:
number: 2
text: The CAR according to claim 1, wherein the transmembrane domain comprises the transmembrane domain of CD28, CD3, CD45, CD4, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, or CD154.
number: 3
text: The CAR according to claim 2, wherein the transmembrane domain comprises the transmembrane domain of CD8.
number: 4
text: The CAR according to any one of claims 1-3, wherein the intracellular signaling domain comprises the intracellular domain of CD3ζ, FcRγ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b or CD66b.
number: 5
text: The CAR according to claim 4, wherein the intracellular signaling domain comprises the intracellular domain of CD3ζ.
number: 6
text: The CAR according to any one of claims 1-5, wherein the CAR further comprises a costimulatory signaling domain, preferably the costimulatory signaling domain comprises the intracellular domain of CD27, CD28, CD137, CD134, CD30, CD40, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, or CD276.
number: 7
text: The CAR according to claim 6, wherein the costimulatory signaling domain comprises the intracellular domain of CD137.
number: 8
text: The CAR according to any one of claims 1-7, wherein the CD1a targeting moiety is a scFV, preferably, the scFV comprises a VL domain consisting of SEQ ID NO: 7 and a VH domain consisting of SEQ ID NO: 8.
number: 9
text: A nucleic acid encoding the CAR according to any one of claims 1-8.
number: 10
text: A cell comprising the nucleic acid according to claim 9 and/or the CAR according to any one of claims 1-8.
number: 11
text: The cell according to claim 10, wherein the cell is a T-cell.
number: 12
text: A pharmaceutical composition comprising a plurality of cells according to claim 11 and a pharmaceutically acceptable carrier or diluent.
number: 13
text: The cell according to claim 11 or the pharmaceutical composition according to claim 12 for use as a medicament.
number: 14
text: The cell according to claim 11 or the pharmaceutical composition according to claim 12 for use in a method of treating a CD1a-positive cancer, wherein the method comprises administering the cell or composition to a patient in need thereof.
number: 15
text: The cell or composition for use according to claim 14, wherein the CD1a-positive cancer is cortical T-cell acute lymphoblastic leukemia, preferably, relapsed/refractory cortical T-cell acute lymphoblastic leukemia.
Office action: search_report, dated 2020-08-19
Rejection reasons: novelty_epc_54
inventive_step_epc_56
Prior art cited: ref_id: US5223409A
ref_type: patent
severity: background
ref_id: WO9218619A1
ref_type: patent
severity: background
ref_id: WO9117271A1
ref_type: patent
severity: background
ref_id: WO9220791A1
ref_type: patent
severity: background
ref_id: WO9215679A1
ref_type: patent
severity: background
ref_id: WO9301288A1
ref_type: patent
severity: background
ref_id: WO9201047A1
ref_type: patent
severity: background
ref_id: WO9209690A2
ref_type: patent
severity: background
ref_id: WO9002809A1
ref_type: patent
severity: background
ref_id: WO2016054555A2
ref_type: patent
severity: background
ref_id: - FREJD & KIM, EXP MOL MED., vol. 49, no. 3, 2017, pages e306
ref_type: npl
severity: background
ref_id: - KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1991, PUBLIC HEALTH SERVICE
ref_type: npl
severity: background
ref_id: - AL-LAZIKANI ET AL., JMB, vol. 273, 1997, pages 927 - 948
ref_type: npl
severity: background
ref_id: - SKERRA, FEBS J., vol. 275, no. 11, 2008, pages 2677 - 83
ref_type: npl
severity: background
ref_id: - RIVIERE; SADELAIN, MOL THER., vol. 25, no. 5, 2017, pages 1117 - 1124
ref_type: npl
severity: background
ref_id: - PLUCKTHUN, ANNU REV PHARMACOL TOXICOL, vol. 55, 2015, pages 489 - 511
ref_type: npl
severity: background
ref_id: - BERTSCHINGER ET AL., PROTEIN ENG DES SEL., vol. 20, no. 2, 2007, pages 57 - 68
ref_type: npl
severity: background
ref_id: - KOIDE ET AL., J MOL BIOL., vol. 415, no. 2, 2013, pages 393 - 405
ref_type: npl
severity: background
ref_id: - BANNAS ET AL., FRONT IMMUNOL., vol. 8, 2017, pages 1603
ref_type: npl
severity: background
ref_id: - REVERDATTO ET AL., CURR TOP MED CHEM., vol. 15, no. 12, 2015, pages 1082 - 101
ref_type: npl
severity: background
ref_id: - "Remington's Pharmaceutical Sciences", 1980
ref_type: npl
severity: background
ref_id: - EUROPEAN JOURNAL OF CANCERS, vol. 45, 2009, pages 228 - 247
ref_type: npl
severity: background
ref_id: - LEE ET AL., PNAS, vol. 109, no. 9, 2012, pages 3299 - 3304
ref_type: npl
severity: background
ref_id: - WEBER, J NUCL MED., vol. 50, 2009, pages 1S - 1 OS
ref_type: npl
severity: background
ref_id: - RICE ET AL., TRENDS GENET, vol. 16, no. 6, 2000, pages 276 - 7
ref_type: npl
severity: background
ref_id: - LI ET AL., NUCLEIC ACIDS RES., vol. 43, no. Wl, 2015, pages W580 - 4
ref_type: npl
severity: background
ref_id: - REITER ET AL., NAT BIOTECHNOL., vol. 14, no. 10, 1996, pages 1239 - 45
ref_type: npl
severity: background
ref_id: - AMIOT M.; BERNARD A.; RAYNAL B.; KNAPP W.; DESCHILDRE C.; BOUMSELL L., J. IMMUNOL., vol. 136, 1986, pages 1752 - 1757
ref_type: npl
severity: background
ref_id: - FURUE M.; NINDL M.; KAWABE K.; NAKAMURA K.; ISHIBASHI Y.; SAGAWA K., J. AM. ACAD. DERMATOL., vol. 27, 1992, pages 419 - 42
ref_type: npl
severity: background
ref_id: - KELLY K. M.; BEVERLY P. C.; CHU A. C.; DAVENPORT V.; GORDON I.; SMITH M.; PRITCHARD J., J. PEDIATR., vol. 125, 1994, pages 717 - 722
ref_type: npl
severity: background
ref_id: - VAN KROONENBURGH M. J.; PAUWELS E. K., NUCL. MED. COMMUN., vol. 9, 1988, pages 919 - 930
ref_type: npl
severity: background
ref_id: - GITANJALI BECHAN; DAVID W. LEE; R. MAARTEN EGELER; ROBERT J. ARCECI, BLOOD, vol. 106, 2005, pages 4815
ref_type: npl
severity: background
ref_id: - BECHAN, G. I.; LEE, D. W.; ZAJONC, D. M.; HECKEL, D.; XIAN, R.; THROSBY, M.; MEIJER, M.; GERMERAAD, W. T.; KRUISBEEK, A. M.; MAART, BR J HAEMATOL, vol. 159, 2012, pages 299 - 310
ref_type: npl
severity: background
ref_id: - FUCHS ET AL., BIO/TECHNOLOGY, vol. 9, 1991, pages 1370 - 1372
ref_type: npl
severity: background
ref_id: - HAY ET AL., HUM ANTIBOD HYBRIDOMAS, vol. 3, 1992, pages 81 - 85
ref_type: npl
severity: background
ref_id: - HUSE ET AL., SCIENCE, vol. 246, 1989, pages 1275 - 1281
ref_type: npl
severity: background
ref_id: - GRIFFTHS ET AL., EMBO J, vol. 12, 1993, pages 725 - 734
ref_type: npl
severity: background
ref_id: - HAWKINS ET AL., J MOL BIOL, vol. 226, 1992, pages 889 - 896
ref_type: npl
severity: background
ref_id: - CLACKSON ET AL., NATURE, vol. 352, 1991, pages 624 - 628
ref_type: npl
severity: background
ref_id: - GRAM ET AL., PNAS, vol. 89, 1992, pages 3576 - 3580
ref_type: npl
severity: background
ref_id: - GARRAD ET AL., BIO/TECHNOLOGY, vol. 9, 1991, pages 1373 - 1377
ref_type: npl
severity: background
ref_id: - HOOGENBOOM ET AL., NUC ACID RES, vol. 19, 1991, pages 4133 - 4137
ref_type: npl
severity: background
ref_id: - BARBAS ET AL., PNAS, vol. 88, 1991, pages 7978 - 7982
ref_type: npl
severity: background
ref_id: - SKRLEC ET AL., TRENDS BIOTECHNOL., vol. 33, no. 7, 2015, pages 408 - 18
ref_type: npl
severity: background
ref_id: - PARRET ET AL., CURR OPIN STRUCT BIOL., vol. 39, 2016, pages 155 - 162
ref_type: npl
severity: background
ref_id: - LIM; JUNE, CELL, vol. 168, no. 4, 2017, pages 724 - 740
ref_type: npl
severity: background
ref_id: - DOHNER H; ESTEY EH; AMADORI S ET AL.: "Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net", BLOOD, vol. 115, 2010, pages 453 - 74
ref_type: npl
severity: background
ref_id: - CHESON BD; BENNETT JM; KOPECKY KJ ET AL.: "Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia", J CLIN ONCOL, vol. 21, 2003, pages 4642 - 9
ref_type: npl
severity: background
ref_id: - CHANTEPIE SP; CORNET E; SALAUN V; REMAN O: "Hematogones: an overview", LEUK RES, vol. 37, 2013, pages 1404 - 11, XP028760892, DOI: doi:10.1016/j.leukres.2013.07.024
ref_type: npl
severity: background
ref_id: - MAUDE SL; FREY N; SHAW PA ET AL.: "Chimeric antigen receptor T cells for sustained remissions in leukemia", N ENGL J MED, vol. 371, 2014, pages 1507 - 17, XP055188099, DOI: doi:10.1056/NEJMoa1407222
ref_type: npl
severity: background
ref_id: - GOKBUGET N; DOMBRET H; BASSAN R; WADLEIGH M; DOUBEK M; RIBERA J: "Inclusion and response criteria for clinical trials in relapsed/refractory acute lymphoblastic leukemia and usefulness of historical control trials", HAEMATOLOGICA., vol. 102, no. 3, 2017, pages eI18 - eI19
ref_type: npl
severity: background
ref_id: - KARRMAN K; JOHANSSON B: "Pediatric T-cell acute lymphoblastic leukemia", GENES CHROMOSOMES CANCER, vol. 56, no. 2, 2017, pages 89 - 116
ref_type: npl
severity: background
ref_id: - WENG AP; FERRANDO AA; LEE W ET AL.: "Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia", SCIENCE, vol. 306, no. 5694, 2004, pages 269 - 271, XP055560772, DOI: doi:10.1126/science.1102160
ref_type: npl
severity: background
ref_id: - HUNGER SP; MULLIGHAN CG: "Acute Lymphoblastic Leukemia in Children", N ENGL J MED., vol. 373, no. 16, 2015, pages 1541 - 1552
ref_type: npl
severity: background
ref_id: - LITZOW MR; FERRANDO AA: "How I treat T-cell acute lymphoblastic leukemia in adults", BLOOD, vol. 126, no. 7, 2015, pages 833 - 841
ref_type: npl
severity: background
ref_id: - SCHNEIDER NR; CARROLL AJ; SHUSTER JJ ET AL.: "New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a pediatric oncology group report of 343 cases", BLOOD, vol. 96, no. 7, 2000, pages 2543 - 2549
ref_type: npl
severity: background
ref_id: - BALLERINI P; LANDMAN-PARKER J; CAYUELA JM ET AL.: "Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome", HAEMATOLOGICA., vol. 93, no. 11, 2008, pages 1658 - 1665
ref_type: npl
severity: background
ref_id: - KARRMAN K; FORESTIER E; HEYMAN M ET AL.: "Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome", GENES CHROMOSOMES CANCER, vol. 48, no. 9, 2009, pages 795 - 805
ref_type: npl
severity: background
ref_id: - SUTTON R; SHAW PJ; VENN NC ET AL.: "Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia", BR J HAEMATOL., vol. 168, no. 3, 2015, pages 395 - 404
ref_type: npl
severity: background
ref_id: - QASIM W; THRASHER AJ: "Progress and prospects for engineered T cell therapies", BR J HAEMATOL., vol. 166, no. 6, 2014, pages 818 - 829
ref_type: npl
severity: background
ref_id: - HUMPHRIES C: "Adoptive cell therapy: Honing that killer instinct", NATURE, vol. 504, no. 7480, 2013, pages 13 - 15
ref_type: npl
severity: background
ref_id: - BRENTJENS RJ; DAVILA ML; RIVIERE I ET AL.: "CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia", SCI TRANSL MED., vol. 5, no. 177, 2013, pages 177ra138, XP055234457, DOI: doi:10.1126/scitranslmed.3005930
ref_type: npl
severity: background
ref_id: - MAUDE SL; FREY N; SHAW PA ET AL.: "Chimeric antigen receptor T cells for sustained remissions in leukemia", NENGL J MED., vol. 371, no. 16, 2014, pages 1507 - 1517, XP055188099, DOI: doi:10.1056/NEJMoa1407222
ref_type: npl
severity: background
ref_id: - GARDNER RA; FINNEY O; ANNESLEY C ET AL.: "Intent-to-treat leukemia remission by CD 19 CAR T cells of defined formulation and dose in children and young adults", BLOOD, vol. 129, no. 25, 2017, pages 3322 - 3331, XP055509718, DOI: doi:10.1182/blood-2017-02-769208
ref_type: npl
severity: background
ref_id: - FRY TJ; SHAH NN; ORENTAS RJ ET AL.: "CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy", NAT MED., vol. 24, no. 1, 2018, pages 20 - 28
ref_type: npl
severity: background
ref_id: - COOPER ML; CHOI J; STASER K ET AL.: "An ''off-the-shelfl fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies", LEUKEMIA, 2018
ref_type: npl
severity: background
ref_id: - GOMES-SILVA D; SRINIVASAN M; SHARMA S ET AL.: "CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies", BLOOD, vol. 130, no. 3, 2017, pages 285 - 296, XP055452686, DOI: doi:10.1182/blood-2017-01-761320
ref_type: npl
severity: background
ref_id: - PNG YT; VINANICA N; KAMIYA T; SHIMASAKI N; COUSTAN-SMITH E; CAMPANA D: "Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies", BLOOD ADV., vol. 1, no. 25, 2017, pages 2348 - 2360, XP055452690, DOI: doi:10.1182/bloodadvances.2017009928
ref_type: npl
severity: background
ref_id: - MAMONKIN M; ROUCE RH; TASHIRO H; BRENNER MK: "A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies", BLOOD., vol. 126, no. 8, 2015, pages 983 - 992, XP055325148, DOI: doi:10.1182/blood-2015-02-629527
ref_type: npl
severity: background
ref_id: - RASAIYAAH J; GEORGIADIS C; PREECE R; MOCK U; QASIM W: "TCRalphabeta/CD3 disruption enables CD3-specific antileukemic T cell immunotherapy", JCIINSIGHT, vol. 3, no. 13, 2018
ref_type: npl
severity: background
ref_id: - MACIOCIA PM; WAWRZYNIECKA PA; PHILIP B ET AL.: "Targeting the T cell receptor beta-chain constant region for immunotherapy of T cell malignancies", NAT MED., vol. 23, no. 12, 2017, pages 1416 - 1423, XP055554554, DOI: doi:10.1038/nm.4444
ref_type: npl
severity: background
ref_id: - BENE MC; CASTOLDI G; KNAPP W ET AL.: "Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL", LEUKEMIA, vol. 9, no. 10, 1995, pages 1783 - 1786, XP008114830
ref_type: npl
severity: background
ref_id: - BURGER R; HANSEN-HAGGE TE; DREXLER HG; GRAMATZKI M: "Heterogeneity of T-acute lymphoblastic leukemia (T-ALL) cell lines: suggestion for classification by immunophenotype and T-cell receptor studies", LEUKRES., vol. 23, no. 1, 1999, pages 19 - 27
ref_type: npl
severity: background
ref_id: - NIEHUES T; KAPAUN P; HARMS DO ET AL.: "A classification based on T cell selection-related phenotypes identifies a subgroup of childhood T-ALL with favorable outcome in the COALL studies", LEUKEMIA, vol. 13, no. 4, 1999, pages 614 - 617, XP009073080, DOI: doi:10.1038/sj/leu/2401374
ref_type: npl
severity: background
ref_id: - VAN GROTEL M; MEIJERINK JP; VAN WERING ER ET AL.: "Prognostic significance of molecularcytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences", LEUKEMIA, vol. 22, no. 1, 2008, pages 124 - 131
ref_type: npl
severity: background
ref_id: - BECHAN GI; LEE DW; ZAJONC DM ET AL.: "Phage display generation of a novel human anti-CDIA monoclonal antibody with potent cytolytic activity", BR J HAEMATOL., vol. 159, no. 3, 2012, pages 299 - 310
ref_type: npl
severity: background
ref_id: - CARRERA SILVA EA; NOWAK W; TESSONE L ET AL.: "CD207(+)CDla(+) cells circulate in pediatric patients with active Langerhans cell histiocytosis", BLOOD, vol. 130, no. 17, 2017, pages 1898 - 1902
ref_type: npl
severity: background
ref_id: - PRIETO C; STAM RW; AGRAZ-DOBLAS A ET AL.: "Activated KRAS Cooperates with MLL-AF4 to Promote Extramedullary Engraftment and Migration of Cord Blood CD34+ HSPC But Is Insufficient to Initiate Leukemia", CANCER RES., vol. 76, no. 8, 2016, pages 2478 - 2489
ref_type: npl
severity: background
ref_id: - MUNOZ-LOPEZ A; VAN ROON EH; ROMERO-MOYA D ET AL.: "Cellular Ontogeny and Hierarchy Influence the Reprogramming Efficiency of Human B Cells into Induced Pluripotent Stem Cells", STEM CELLS, vol. 34, no. 3, 2016, pages 581 - 587
ref_type: npl
severity: background
ref_id: - MUNOZ-LOPEZ A; ROMERO-MOYA D; PRIETO C ET AL.: "Development Refractoriness of MLLRearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency", STEM CELL REPORTS, vol. 7, no. 4, 2016, pages 602 - 618
ref_type: npl
severity: background
ref_id: - BUENO C; ROLDAN M; ANGUITA E ET AL.: "Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease", HAEMATOLOGICA, vol. 99, no. 7, 2014, pages 1168 - 1175
ref_type: npl
severity: background
ref_id: - MENENDEZ P; CATALINA P; RODRIGUEZ R ET AL.: "Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene", J EXP MED., vol. 206, no. 13, 2009, pages 3131 - 3141
ref_type: npl
severity: background
ref_id: - RODRIGUEZ R; TORNIN J; SUAREZ C ET AL.: "Expression of FUS-CHOP fusion protein in immortalized/transformed human mesenchymal stem cells drives mixoid liposarcoma formation", STEM CELLS, vol. 31, no. 10, 2013, pages 2061 - 2072
ref_type: npl
severity: background
ref_id: - RECASENS-ZORZO C; CARDESA-SALZMANN T; PETAZZI P ET AL.: "Pharmacological modulation of CXCR4 cooperates with BET bromodomain inhibition in diffuse large B-cell lymphoma", HAEMATOLOGICA, 2018
ref_type: npl
severity: background
ref_id: - GARCIA-PEYDRO M; FUENTES P; MOSQUERA M ET AL.: "The NOTCH1/CD44 axis drives pathogenesis in a T cell acute lymphoblastic leukemia model", J CLIN INVEST., 2018
ref_type: npl
severity: background
ref_id: - DALMAU J; ROTGER M; ERKIZIA I ET AL.: "Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression", AIDS, vol. 28, no. 9, 2014, pages 1261 - 1272
ref_type: npl
severity: background
ref_id: - ADDO MM; YU XG; RATHOD A ET AL.: "Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV -1 )-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load", J VIROL., vol. 77, no. 3, 2003, pages 2081 - 2092, XP002291386, DOI: doi:10.1128/JVI.77.3.2081-2092.2003
ref_type: npl
severity: background
ref_id: - MARTIN-GAYO E; GONZALEZ-GARCIA S; GARCIA-LEON MJ ET AL.: "Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches", J EXP MED., vol. 214, no. 11, 2017, pages 3361 - 3379
ref_type: npl
severity: background
ref_id: - GALY A; VERMA S; BARCENA A; SPITS H: "Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development", J EXP MED., vol. 178, no. 2, 1993, pages 391 - 401
ref_type: npl
severity: background
ref_id: - LEPRETRE S; GRAUX C; TOUZART A; MACINTYRE E; BOISSEL N: "Adult T-type lymphoblastic lymphoma: Treatment advances and prognostic indicators", EXP HEMATOL., vol. 51, 2017, pages 7 - 16, XP085076729, DOI: doi:10.1016/j.exphem.2017.04.002
ref_type: npl
severity: background
ref_id: - MARKS DI; PAIETTA EM; MOORMAN AV ET AL.: "T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993", BLOOD, vol. 114, no. 25, 2009, pages 5136 - 5145
ref_type: npl
severity: background
ref_id: - MENDES RD; CANTE-BARRETT K; PIETERS R; MEIJERINK JP: "The relevance of PTEN-AKT in relation to NOTCH1-directed treatment strategies in T-cell acute lymphoblastic leukemia", HAEMATOLOGICA, vol. 101, no. 9, 2016, pages 1010 - 1017
ref_type: npl
severity: background
ref_id: - LEMAISTRE CF; ROSEN S; FRANKEL A ET AL.: "Phase I trial of H65-RTA immunoconjugate in patients with cutaneous T-cell lymphoma", BLOOD, vol. 78, no. 5, 1991, pages 1173 - 1182
ref_type: npl
severity: background
ref_id: - FRANKEL AE; LAVER JH; WILLINGHAM MC; BURNS LJ; KERSEY JH; VALLERA DA: "Therapy of patients with T-cell lymphomas and leukemias using an anti-CD7 monoclonal antibody-ricin A chain immunotoxin", LEUK LYMPHOMA, vol. 26, no. 3-4, 1997, pages 287 - 298
ref_type: npl
severity: background
ref_id: - JUNCA J; BOTIN T; VILA J; NAVARRO JT; MILLA F: "Adult T-cell leukemia/lymphoma with an unusual CDla positive phenotype", CYTOMETRY B CLIN CYTOM., vol. 86, no. 4, 2014, pages 292 - 296
ref_type: npl
severity: background
ref_id: - VAN DEN BROEK T; MADI A; DELEMARRE EM ET AL.: "Human neonatal thymectomy induces altered Bcell responses and autoreactivity", EUR J IMMUNOL., vol. 47, no. 11, 2017, pages 1970 - 1981
ref_type: npl
severity: background
ref_id: - KUROBE H; TOMINAGA T; SUGANO M ET AL.: "Complete but not partial thymectomy in early infancy reduces T-cell-mediated immune response: three-year tracing study after pediatric cardiac surgery", J THORAC CARDIOVASC SURG, vol. 145, no. 3, 2013, pages 656 - 662, XP028979734, DOI: doi:10.1016/j.jtcvs.2012.12.015
ref_type: npl
severity: background
ref_id: - VAN DEN BROEK T; DELEMARRE EM; JANSSEN WJ ET AL.: "Neonatal thymectomy reveals differentiation and plasticity within human naive T cells", J CLIN INVEST., vol. 126, no. 3, 2016, pages 1126 - 1136
ref_type: npl
severity: background
ref_id: [XYI]     - MENENDEZ PABLO ET AL: "Adoptive Cellular Immunotherapy Using Cd1a CART-Cells for Cortical T-Cell Acute Lymphoblastic Leukemia", EXPERIMENTAL HEMATOLOGY, ELSEVIER INC, US, vol. 64, 22 August 2018 (2018-08-22), XP085449254, ISSN: 0301-472X, DOI: 10.1016/J.EXPHEM.2018.06.089
ref_type: npl
severity: background
ref_id: - MILIOTOU N. ANDROULLA ET AL: "CAR T-cell Therapy: A New Era in Cancer Immunotherapy", CURRENT PHARMACEUTICAL BIOTECHNOLOGY, vol. 19, no. 1, 31 May 2018 (2018-05-31), NL, pages 5 - 18, XP055560547, ISSN: 1389-2010, DOI: 10.2174/1389201019666180418095526
ref_type: npl
severity: background
ref_id: - SAMUEL MURRAY ET AL: "Diagnostic and Therapeutic Evaluation of an Anti-Langerhans Cell Histiocytosis Monoclonal Antibody (NA1/34) in a New Xenograft Model", JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 114, no. 1, 1 January 2000 (2000-01-01), NL, pages 127 - 134, XP055606701, ISSN: 0022-202X, DOI: 10.1046/j.1523-1747.2000.00831.x
ref_type: npl
severity: background
ref_id: - N.N.: "CD1A (NA1/34): sc-53035", SANTA CRUZ BIOTECHNOLOGY: ONLINE CATALOGUE, 25 April 2017 (2017-04-25), pages 1 - 1, XP055606820, Retrieved from the Internet <URL:https://datasheets.scbt.com/sc-53035.pdf> [retrieved on 20190718]
ref_type: npl
severity: background
ref_id: [XYI]     - D SANCHEZ-MARTINEZ ET AL: "Adoptive Cellular Immunotherapy using CD1a CART-cells for Treatment of Cortical Pediatric T-Cell Acute Lymphoblastic Leukemia", KLINISCHE PAEDIATRIE, vol. 230, no. 3, 1 April 2018 (2018-04-01), DE, pages 174, XP055606754, ISSN: 1439-3824, DOI: 10.1055/s-0038-1645020
ref_type: npl
severity: background
ref_id: - DIEGO ANCHEZ-MARTÍNEZ ET AL: "Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia", 23 May 2019 (2019-05-23), pages 2291 - 2304, XP055606731, Retrieved from the Internet <URL:http://www.bloodjournal.org/content/bloodjournal/133/21/2291.full.pdf> [retrieved on 20190718]
ref_type: npl
severity: background
ref_id: - MENENDEZ PABLO ET AL, "Adoptive Cellular Immunotherapy Using Cd1a CART-Cells for Cortical T-Cell Acute Lymphoblastic Leukemia", EXPERIMENTAL HEMATOLOGY, ELSEVIER INC, US, (20180822), vol. 64, doi:10.1016/J.EXPHEM.2018.06.089, ISSN 0301-472X, XP085449254 [X] 1,9-11 * abstract * [Y] 2-8 [I] 12-15
ref_type: npl
severity: novelty_destroying
ref_id: - MILIOTOU N. ANDROULLA ET AL, "CAR T-cell Therapy: A New Era in Cancer Immunotherapy", CURRENT PHARMACEUTICAL BIOTECHNOLOGY, NL, (20180531), vol. 19, no. 1, doi:10.2174/1389201019666180418095526, ISSN 1389-2010, pages 5 - 18, XP055560547 [Y] 2-7 * figure 1 *
ref_type: npl
severity: obviousness
ref_id: - SAMUEL MURRAY ET AL, "Diagnostic and Therapeutic Evaluation of an Anti-Langerhans Cell Histiocytosis Monoclonal Antibody (NA1/34) in a New Xenograft Model", JOURNAL OF INVESTIGATIVE DERMATOLOGY, NL, (20000101), vol. 114, no. 1, doi:10.1046/j.1523-1747.2000.00831.x, ISSN 0022-202X, pages 127 - 134, XP055606701 [Y] 8 * abstract *
ref_type: npl
severity: obviousness
ref_id: - N.N., "CD1A (NA1/34): sc-53035", Santa Cruz Biotechnology: online catalogue, (20170425), pages 1 - 1, URL: https://datasheets.scbt.com/sc-53035.pdf, (20190718), XP055606820 [Y] 8 * the whole document *
ref_type: npl
severity: obviousness
ref_id: - D SANCHEZ-MARTINEZ ET AL, "Adoptive Cellular Immunotherapy using CD1a CART-cells for Treatment of Cortical Pediatric T-Cell Acute Lymphoblastic Leukemia", KLINISCHE PAEDIATRIE, DE, (20180401), vol. 230, no. 3, doi:10.1055/s-0038-1645020, ISSN 1439-3824, page 174, XP055606754 [X] 1,9-11 * the whole document * [Y] 2-8 [I] 12-15
ref_type: npl
severity: novelty_destroying
ref_id: - Diego Anchez-Martínez ET AL, "Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia", (20190523), pages 2291 - 2304, URL: http://www.bloodjournal.org/content/bloodjournal/133/21/2291.full.pdf, (20190718), XP055606731 [T] * the whole document *
ref_type: npl
severity: background
Final disposition: pending (2020-08-19)