Chimeric antigen receptor T cell therapy: 25 years in the making

Blood Reviews

Volumn 30, Issue 3, 2016, Pages 157-167

  Gill, Saar ^a   Maus, Marcela V ^a   Porter, David L ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Adoptive immunotherapy; Chimeric antigen receptor T cells

Indexed keywords

CD19 ANTIGEN; CHIMERIC ANTIGEN RECEPTOR; VIRUS VECTOR; HYBRID PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR;

ACUTE MYELOBLASTIC LEUKEMIA; ADOPTIVE TRANSFER; B CELL LEUKEMIA; CELL EXPANSION; CELL PROLIFERATION; CELL THERAPY; CELLULAR IMMUNITY; CLINICAL EFFECTIVENESS; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; INTRACELLULAR SIGNALING; MYELOMA; NONHUMAN; OUTCOME ASSESSMENT; PATIENT SAFETY; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; ADOPTIVE IMMUNOTHERAPY; ANIMAL; BIOLOGICAL THERAPY; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; NEOPLASM; PROCEDURES; TRENDS;

ANIMALS; CELL- AND TISSUE-BASED THERAPY; HUMANS; IMMUNOTHERAPY; IMMUNOTHERAPY, ADOPTIVE; NEOPLASMS; RECEPTORS, ANTIGEN, T-CELL; RECOMBINANT FUSION PROTEINS; T-LYMPHOCYTES;

EID: 84960937874     PISSN: 0268960X     EISSN: 15321681     Source Type: Journal    
DOI: 10.1016/j.blre.2015.10.003     Document Type: Review

References (102)

1. Gross G., Waks T., Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A 1989, 86(24):10024-10028.
2. Amado R.G., Chen I.S.Y. Lentiviral vectors-the promise of gene therapy within reach?. Science 1999, 285(5428):674-676. [80-]. 10.1126/science.285.5428.674.
3. Naldini L., Blömer U., Gallay P., et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996, 272(5259):263-267.
4. Hacein-Bey-Abina S., Von Kalle C., Schmidt M., et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003, 302(5644):415-419. 10.1126/science.1088547.
5. Ellis J. Silencing and variegation of gammaretrovirus and lentivirus vectors. Hum Gene Ther 2005, 16(11):1241-1246. 10.1089/hum.2005.16.1241.
6. Scholler J., Brady T.L., Binder-Scholl G., et al. Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci Transl Med 2012, 4(132):132ra53. 10.1126/scitranslmed.3003761.
7. Dupuy A.J., Akagi K., Largaespada D.A., Copeland N.G., Jenkins N.A. Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system. Nature 2005, 436(7048):221-226. 10.1038/nature03691.
8. Hackett P.B., Largaespada D.A., Cooper L.J.N. A transposon and transposase system for human application. Mol Ther 2010, 18(4):674-683. 10.1038/mt.2010.2.
9. Kebriaei P., Huls H., Jena B., et al. Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies. Hum Gene Ther 2012, 23(5):444-450. 10.1089/hum.2011.167.
10. Hackett P.B., Largaespada D.A., Switzer K.C., LJN C. Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy. Transl Res 2013, 161(4):265-283. 10.1016/j.trsl.2012.12.005.
11. Zhao Y., Moon E., Carpenito C., Paulos C.M., Liu X. Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res 2010, 70:9053-9061. 10.1158/0008-5472.CAN-10-2880.
12. Beatty G.L., Haas A.R., Maus M.V., et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2014, 2(2):112-120. 10.1158/2326-6066.CIR-13-0170.
13. Krebs S., Chow K.K.H., Yi Z., et al. T cells redirected to interleukin-13Rα2 with interleukin-13 mutein-chimeric antigen receptors have anti-glioma activity but also recognize interleukin-13Rα1. Cytotherapy 2014, 16(8):1121-1131. 10.1016/j.jcyt.2014.02.012.
14. Rapoport A.P., Stadtmauer E.A., Binder-Scholl G.K., et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med 2015, 21(8):1-10. 10.1038/nm.3910.
15. Milone M.C., Fish J.D., Carpenito C., et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther 2009, 17(8):1453-1464. 10.1038/mt.2009.83.
16. Savoldo B., Ramos C.A., Liu E., et al. Brief report CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 2011, 121(5):1822-1826. 10.1172/JCI46110DS1.
17. Long A.H., Haso W.M., Shern J.F., et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med 2015, 21(6):581-590. 10.1038/nm.3838.
18. Porter D.L., Levine B.L., Kalos M., Bagg A., June C.H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011, 365(8):725-733. 10.1056/NEJMoa1103849.
19. Hollyman D., Stefanski J., Przybylowski M., et al. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. J Immunother 2009, 32(2):169-180. 10.1097/CJI.0b013e318194a6e8.
20. Micklethwaite K.P., Savoldo B., Hanley P.J., et al. Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation. Blood 2010, 115(13):2695-2703. 10.1182/blood-2009-09-242263.
21. Jensen M.C., Popplewell L., Cooper L.J., et al. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol Blood Marrow Transplant 2010, 16(9):1245-1256. 10.1016/j.bbmt.2010.03.014.
22. Johnson L.A., Morgan R.A., Dudley M.E., et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009, 114(3):535-546. 10.1182/blood-2009-03-211714.
23. Maus M.V., Thomas A.K., Leonard D.G.B., et al. Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB. Nat Biotechnol 2002, 20(2):143-148. 10.1038/nbt0202-143.
24. Singh H., Figliola M.J., Dawson M.J., et al. Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignancies. Cancer Res 2011, 71(10):3516-3527. 10.1158/0008-5472.CAN-10-3843.
25. Porter D.L., Levine B.L., Bunin N., et al. A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood 2006, 107(4):1325-1331. 10.1182/blood-2005-08-3373.
26. Brentjens R.J., Riviere I., Park J.H., et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 2011, 118(18):4817-4828. 10.1182/blood-2011-04-348540.
27. Jensen M.C., Clarke P., Tan G., et al. Human T lymphocyte genetic modification with naked DNA. Mol Ther 2000, 1(1):49-55. 10.1006/mthe.1999.0012.
28. Kochenderfer J.N., Dudley M.E., Feldman S.A., et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 2012, 119(12):2709-2720. 10.1182/blood-2011-10-384388.
29. Ye Q., Loisiou M., Levine B.L., et al. Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes. J Transl Med 2011, 9(1):131. 10.1186/1479-5876-9-131.
30. Xu Y., Zhang M., Ramos C.A., et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood 2014, 123(24):3750-3759. 10.1182/blood-2014-01-552174.
31. Riddell S.R., Sommermeyer D., Berger C., et al. Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition. Cancer J 2014, 20(2):141-144.
32. Dudley M.E., Wunderlich J.R., Yang J.C., et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005, 23(10):2346-2357. 10.1200/JCO.2005.00.240.
33. Kershaw M.H., Westwood J.A., Parker L.L., et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 2006, 12(20):6106-6115. 10.1158/1078-0432.CCR-06-1183.
34. Ritchie D.S., Neeson P.J., Khot A., et al. Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 2013, 21(11):2122-2129. 10.1038/mt.2013.154.
35. Kalos M., Levine B.L., Porter D.L., et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011, 3(95):95ra73. 10.1126/scitranslmed.3002842.
36. Moon E.K., Carpenito C., Sun J., et al. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human t cells expressing a mesothelin-specific chimeric antibody receptor. Clin Cancer Res 2011, 17(14):4719-4730. 10.1158/1078-0432.CCR-11-0351.
37. Fridman W.H., Pagès F., Sautès-Fridman C., Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012, 12(4):298-306. 10.1038/nrc3245.
38. John L.B., Devaud C., Duong C.P.M., et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 2013, 19(20):5636-5646. 10.1158/1078-0432.CCR-13-0458.
39. Moon E.K., Wang L.-C.S., Dolfi D.V., et al. Multifactorial T cell hypofunction that is reversible can limit the efficacy of chimeric antibody receptor-transduced human T cells in solid tumors. Clin Cancer Res 2014, 20(16):4262-4273. 10.1158/1078-0432.CCR-13-2627.
40. Perna S.K., Pagliara D., Mahendravada A., et al. Interleukin-7 mediates selective expansion of tumor-redirected cytotoxic T lymphocytes (CTLs) without enhancement of regulatory T-cell inhibition. Clin Cancer Res 2013, 20:131-139.
41. Grupp S.A., Kalos M., Barrett D., et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013, 368(16):1509-1518. 10.1056/NEJMoa1215134.
42. Lamers C.H.J., Sleijfer S., Vulto A.G., et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol 2006, 24(13):e20-e22. 10.1200/JCO.2006.05.9964.
43. Maude S.L., Frey N., Shaw P.A., et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014, 371(16):1507-1517. 10.1056/NEJMoa1407222.
44. Lee D.W., Kochenderfer J.N., Stetler-Stevenson M., et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015, 385(14):517-528. 10.1016/S0140-6736(14)61403-3.
45. Kochenderfer J.N., Rosenberg S.A. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 2013, 10(5):267-276. 10.1038/nrclinonc.2013.46.
46. Till B.G., Jensen M.C., Wang J., et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 2008, 112(6):2261-2271. 10.1182/blood-2007-12-128843.
47. Kochenderfer J.N., Wilson W.H., Janik J.E., et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010, 116(20):4099-4102. 10.1182/blood-2010-04-281931.
48. Kochenderfer J.N., Dudley M.E., Kassim S.H., et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2015, 33(6):540-549. 10.1200/JCO.2014.56.2025.
49. Davila M.L., Riviere I., Wang X., et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014, 6(224):224ra25. 10.1126/scitranslmed.3008226.
50. Kochenderfer J.N., Dudley M.E., Carpenter R.O., et al. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 2013, 122(25):4129-4139. 10.1182/blood-2013-08-519413.
51. Cruz C.R.Y., Micklethwaite K.P., Savoldo B., et al. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood 2013, 122(17):2965-2973. 10.1182/blood-2013-06-506741.
52. Lee D.W., Gardner R., Porter D.L., et al. How I treat current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014, 124(2):188-195. 10.1182/blood-2014-05-552729.current.
53. Haso W., Lee D.W., Shah N.N., et al. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 2013, 121(7):1165-1174. 10.1182/blood-2012-06-438002.
54. Giordano Attianese G.M.P., Marin V., Hoyos V., et al. In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor. Blood 2011, 117(18):4736-4745. 10.1182/blood-2010-10-311845.
55. Hudecek M., Schmitt T.M., Baskar S., et al. The B-cell tumor-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor. Blood 2010, 116(22):4532-4541. 10.1182/blood-2010-05-283309.
56. Vera J., Savoldo B., Vigouroux S., et al. T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells T lymphocytes redirected against the light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived. Blood 2006, 108:3890-3897. 10.1182/blood-2006-04-017061.
57. Ramos C.A., Savoldo B., Liu E., et al. Clinical responses in patients infused with t lymphocytes redirected to target kappa-light immunoglobulin chain. American Society of Hematology Annual Meeting Proceedings 2013, 20:S26.
58. Gill S., Tasian S.K., Ruella M., et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood 2014, 123(15):2343-2354. 10.1182/blood-2013-09-529537.
59. Mardiros A., Dos Santos C., McDonald T., et al. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and anti-tumor effects against human acute myeloid leukemia. Blood 2013, 122(18):3138-3148. 10.1182/blood-2012-12-474056.
60. Frankel A.E., Woo J.H., Ahn C., et al. Activity of SL-401, a targeted therapy directed to the interleukin-3 receptor, in patients with blastic plasmacytoid dendritic cell neoplasm. Blood 2014, [prepublish]. 10.1182/blood-2014-04-566737.
61. Burnett A.K., Hills R.K., Milligan D., et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol 2011, 29(4):369-377. 10.1200/JCO.2010.31.4310.
62. Fayad L., Offner F., Smith M.R., et al. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol 2013, 31(5):573-583. 10.1200/JCO.2012.42.7211.
63. Pizzitola I., Anjos-Afonso F., Rouault-Pierre K., et al. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia 2014, 28(8):1596-1605. 10.1038/leu.2014.62.
64. Kenderian S.S., Ruella M., Shestova O., et al. CD33 specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia 2015, [epub ahead]. 10.1038/leu.2015.52.
65. Wang Q., Wang Y., Lv H., et al. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther 2014, 23(1):184-191. 10.1038/mt.2014.164.
66. Casucci M., Nicolis B., Falcone L., et al. Myeloid leukemia and multiple myeloma CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 2013, 122:3461-3472. 10.1182/blood-2013-04-493361.
67. Tijink B.M., Buter J., de Bree R., et al. A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res 2006, 12(20):6064-6072. 10.1158/1078-0432.CCR-06-0910.
68. Savoldo B., Rooney C.M., Di Stasi A., et al. Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood 2007, 110(7):2620-2630. 10.1182/blood-2006-11-059139.
69. Hombach A., Heuser C., Sircar R., et al. Characterization of a chimeric T cell receptor with specificity for the Hodgkin's lymphoma-associated CD30 antigen. J Immunother 1999, 22(6):473-480.
70. Mamonkin M., Rouce R.H., Tashiro H., Brenner M.K. A T cell-directed chimeric antigen receptor for the selective treatment of T cell malignancies. Blood 2015, 10.1182/blood-2015-02-629527.
71. Chang Y., Connolly J., Shimasaki N., Mimura K., Kono K., Campana D. A chimeric receptor with NKG2D specificity enhances natural killer cell activation and killing of tumor cells natural killer cell activation and killing of tumor cells. Cancer Res 2013, 73:1777-1786. 10.1158/0008-5472.CAN-12-3558.
72. Ocqueteau M., San Miguel J.F., González M., Almeida J., Orfao A. Do myelomatous plasma cells really express surface immunoglobulins?. Haematologica 1996, 81(5):460-463. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8952161.
73. Bernfield M., Kokenyesi R., Kato M., et al. Biology of the syndecans: a family of transmembrane heparan sulfate proteoglycans. Annu Rev Cell Biol 1992, 8:365-393.
74. Wijdenes J., Vooijs W., Clement C., et al. A plasmocyte selective monoclonal antibody (B-B4) recognizes syndecan-1. Br J Haematol 1996, 94(2):318-323.
75. O'Connell F.P., Pinkus J.L., Pinkus G.S. CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. Am J Clin Pathol 2004, 121(2):254-263. 10.1309/617DWB5GNFWXHW4L.
76. Heffner L.T., Jagannath S., Zimmerman T.M., et al. BT062, an antibody-drug conjugate directed against CD138, given weekly for 3 weeks in each 4 week cycle: safety and further evidence of clinical activity. American Society of Hematology Annual Meeting Proceedings 2012, vol. 120:653.
77. O'Connor B., Raman V., Erickson L., et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med 2004, 199:91-98.
78. Novak A.J., Darce J.R., Arendt B.K., et al. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood 2004, 103(2):689-694. 10.1182/blood-2003-06-2043.
79. Hsi E.D., Steinle R., Balasa B., et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res 2008, 14(9):2775-2784. 10.1158/1078-0432.CCR-07-4246.
80. Zonder J.A., Mohrbacher A.F., Singhal S., et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 2012, 120(3):552-559. 10.1182/blood-2011-06-360552.
81. Chu J., Deng Y., Benson D.M., et al. CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia 2014, 28(4):917-927. 10.1038/leu.2013.279.
82. Chu J., He S., Deng Y., et al. Genetic modification of T cells redirected towards CS1 enhances eradication of myeloma cells. Clin Cancer Res 2014, 20(15):3989-4000. 10.1158/1078-0432.CCR-13-2510.
83. Mihara K., Bhattacharyya J., Kitanaka A., et al. T-cell immunotherapy with a chimeric receptor against CD38 is effective in eliminating myeloma cells. Leukemia 2012, 26(2):365-367. 10.1038/leu.2011.205.
84. Manz M.G., Miyamoto T., Akashi K., Weissman I.L. Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci U S A 2002, 99(18):11872-11877. 10.1073/pnas.172384399.
85. Plesner T., Lokhorst H.M., Gimsing P., Nahi H., Lisby S., Richardson P.G. Daratumumab, a CD38 monoclonal antibody in patients with multiple myeloma-data from a dose-escalation phase I/II study. American Society of Hematology Annual Meeting Proceedings 2012, vol. 120:73.
86. Garfall A.L., Maus M.V., Hwang W.-T., et al. Chimeric antigen receptor T cells against CD19 for multiple myeloma. N Engl J Med 2015, 373(11):1040-1047. 10.1056/NEJMoa1504542.
87. Morgan R.A., Yang J.C., Kitano M., Dudley M.E., Laurencot C.M., Rosenberg S.A. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010, 18(4):843-851. 10.1038/mt.2010.24.
88. Ahmed N., Brawley V.S., Hegde M., et al. Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol 2015, 33(15):1688-1696. 10.1200/JCO.2014.58.0225.
89. Lamers C.H., Sleijfer S., van Steenbergen S., et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther 2013, 21(4):904-912. 10.1038/mt.2013.17.
90. Kloss C.C., Condomines M., Cartellieri M., Bachmann M., Sadelain M. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol 2013, 31(1):71-75. 10.1038/nbt.2459.
91. Wilkie S., MCI Van S., Hobbs S., et al. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J Clin Immunol 2012, 32:1059-1070. 10.1007/s10875-012-9689-9.
92. Hassan R., Cohen S.J., Phillips M., et al. Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clin Cancer Res 2010, 16(24):6132-6138. 10.1158/1078-0432.CCR-10-2275.
93. Hassan R., Miller A.C., Sharon E., et al. Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci Transl Med 2013, 5(208):208ra147. 10.1126/scitranslmed.3006941.
94. Maus M.V., Haas A.R., Beatty G.L., et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res 2013, 1:26-31.
95. Brown C.E., Badie B., Barish M.E., et al. Bioactivity and safety of IL13R 2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res 2015, 10.1158/1078-0432.CCR-15-0428.
96. Katz S.C., Burga R.A., McCormack E., et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor modified T cell therapy for CEA+ liver metastases. Clin Cancer Res 2015, 20:1-12. 10.1158/1078-0432.CCR-14-1421.
97. Koneru M., O'Cearbhaill R., Pendharkar S., Spriggs D.R., Brentjens R.J. A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16ecto directed chimeric antigen receptors for recurrent ovarian cancer. J Transl Med 2015, 13(1). 10.1186/s12967-015-0460-x.
98. Kakarla S., Chow K.K., Mata M., et al. Antitumor effects of chimeric receptor engineered human T cells directed to tumor stroma. Mol Ther 2013, 21(8):1611-1620. 10.1038/mt.2013.110.
99. Tran E., Chinnasamy D., Yu Z., et al. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia. J Exp Med 2013, 210(6):1125-1135. 10.1084/jem.20130110.
100. Lamers C.H.J., Gratama J.W., Pouw N.M.C., et al. Parallel detection of transduced T lymphocytes after immunogene therapy of renal cell cancer by flow cytometry and real-time polymerase chain reaction: implications for loss of transgene expression. Hum Gene Ther 2005, 16(12):1452-1462. 10.1089/hum.2005.16.1452.
101. Westwood J.A., Smyth M.J., MWL T., et al. Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of lewis-Y-expressing tumors in mice. Proc Natl Acad Sci U S A 2005, 102(52):19051-19056. 10.1073/pnas.0504312102.
102. Ramsay A.G., Clear A.J., Fatah R., Gribben J.G., Dc W. Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer. Blood 2012, 120(7):1412-1421. 10.1182/blood-2012-02-411678.