Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma

Science Translational Medicine

Volumn 7, Issue 275, 2015, Pages

  Johnson, Laura A ^a,b   Scholler, John ^a   Ohkuri, Takayuki ^c   Kosaka, Akemi ^c   Patel, Prachi R ^a   McGettigan, Shannon E ^a   Nace, Arben K ^b   Dentchev, Tzvete ^b   Thekkat, Pramod ^d   Loew, Andreas ^d   Boesteanu, Alina C ^a   Cogdill, Alexandria P ^a   Chen, Taylor ^a   Fraietta, Joseph A ^a   Kloss, Christopher C ^a   Posey, Avery D ^a   Engels, Boris ^d   Singh, Reshma ^d   Ezell, Tucker ^d   Idamakanti, Neeraja ^d   Ramones, Melissa H ^d   Li, Na ^d   Zhou, Li ^d   Plesa, Gabriela ^a   Seykora, John T ^b   Okada, Hideho ^e   June, Carl H ^a,b   Brogdon, Jennifer L ^d   Maus, Marcela V ^a   more..

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CETUXIMAB; CHIMERIC ANTIGEN RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR VARIANT III CHIMERIC ANTIGEN RECEPTOR; GAMMA INTERFERON; INTERLEUKIN 2; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; TEMOZOLOMIDE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; LYMPHOCYTE ANTIGEN RECEPTOR;

ADOPTIVE IMMUNOTHERAPY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; CANCER RECURRENCE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOLYSIS; DISEASE MODEL; DRUG TARGETING; GENETIC TRANSDUCTION; GLIOBLASTOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; KERATINOCYTE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; RECEPTOR BINDING; SKIN TRANSPLANTATION; T LYMPHOCYTE; TUMOR XENOGRAFT; WILD TYPE; ANIMAL; BRAIN NEOPLASMS; IMMUNOLOGY; IMMUNOTHERAPY; XENOGRAFT;

ANIMALS; BRAIN NEOPLASMS; DISEASE MODELS, ANIMAL; GLIOBLASTOMA; HETEROGRAFTS; HUMANS; IMMUNOTHERAPY; MICE; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTORS, ANTIGEN, T-CELL;

EID: 84923078274     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aaa4963     Document Type: Article

References (53)

1. F. S. Hodi, S. J. O'Day, D. F. McDermott, R. W. Weber, J. A. Sosman, J. B. Haanen, R. Gonzalez, C. Robert, D. Schadendorf, J. C. Hassel, W. Akerley, A. J. van den Eertwegh, J. Lutzky, P. Lorigan, J. M. Vaubel, G. P. Linette, D. Hogg, C. H. Ottensmeier, C. Lebbe, C. Peschel, I. Quirt, J. I. Clark, J. D. Wolchok, J. S. Weber, J. Tian, M. J. Yellin, G. M. Nichol, A. Hoos, W. J. Urba, Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711-723 (2010).
2. S. L. Topalian, F. S. Hodi, J. R. Brahmer, S. N. Gettinger, D. C. Smith, D. F. McDermott, J. D. Powderly, R. D. Carvajal, J. A. Sosman, M. B. Atkins, P. D. Leming, D. R. Spigel, S. J. Antonia, L. Horn, C. G. Drake, D. M. Pardoll, L. Chen, W. H. Sharfman, R. A. Anders, J. M. Taube, T. L. McMiller, H. Xu, A. J. Korman, M. Jure-Kunkel, S. Agrawal, D. McDonald, G. D. Kollia, A. Gupta, J. M. Wigginton, M. Sznol, Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454 (2012).
3. D. L. Porter, B. L. Levine, M. Kalos, A. Bagg, C. H. June, Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365, 725-733 (2011).
4. S. A. Grupp, M. Kalos, D. Barrett, R. Aplenc, D. L. Porter, S. R. Rheingold, D. T. Teachey, A. Chew, B. Hauck, J. F. Wright, M. C. Milone, B. L. Levine, C. H. June, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 368, 1509-1518 (2013).
5. S. L. Maude, N. Frey, P. A. Shaw, R. Aplenc, D. M. Barrett, N. J. Bunin, A. Chew, V. E. Gonzalez, Z. Zheng, S. F. Lacey, Y. D. Mahnke, J. J. Melenhorst, S. R. Rheingold, A. Shen, D. T. Teachey, B. L. Levine, C. H. June, D. L. Porter, S. A. Grupp, Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371, 1507-1517 (2014).
6. C. H. Lamers, S. Sleijfer, A. G. Vulto, W. H. Kruit, M. Kliffen, R. Debets, J. W. Gratama, G. Stoter, E. Oosterwijk, Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: First clinical experience. J. Clin. Oncol. 24, e20-e22 (2006).
7. R. A. Morgan, J. C. Yang, M. Kitano, M. E. Dudley, C. M. Laurencot, S. A. Rosenberg, Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18, 843-851 (2010).
8. R. A. Morgan, N. Chinnasamy, D. Abate-Daga, A. Gros, P. F. Robbins, Z. Zheng, M. E. Dudley, S. A. Feldman, J. C. Yang, R. M. Sherry, G. Q. Phan, M. S. Hughes, U. S. Kammula, A. D. Miller, C. J. Hessman, A. A. Stewart, N. P. Restifo, M. M. Quezado, M. Alimchandani, A. Z. Rosenberg, A. Nath, T. Wang, B. Bielekova, S. C. Wuest, N. Akula, F. J. McMahon, S. Wilde, B. Mosetter, D. J. Schendel, C. M. Laurencot, S. A. Rosenberg, Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J. Immunother. 36, 133-151 (2013).
9. K. J. Hatanpaa, S. Burma, D. Zhao, A. A. Habib, Epidermal growth factor receptor in glioma: Signal transduction, neuropathology, imaging, and radioresistance. Neoplasia 12, 675-684 (2010).
10. P. Gupta, S.-Y. Han, M. Holgado-Madruga, S. Mitra, G. Li, R. Nitta, A. Wong, Development of an EGFRvIII specific recombinant antibody. BMC Biotechnol. 10, 72 (2010).
11. A. Wong, S. Bigner, D. Bigner, K. Kinzler, S. Hamilton, B. Vogelstein, Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc. Natl. Acad. Sci. U.S.A. 84, 6899-6903 (1987).
12. B. Friguet, A. Chaffotte, L. Djavadi-Ohaniance, M. Goldberg, Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay. J. Immunol. Methods 77, 305-319 (1985).
13. A. Mukasa, J. Wykosky, K. Ligon, L. Chin, W. Cavenee, F. Furnari, Mutant EGFR is required for maintenance of glioma growth in vivo, and its ablation leads to escape from receptor dependence. Proc. Natl. Acad. Sci. U.S.A. 107, 2616-2621 (2010).
14. M. M. Feldkamp, P. Lala, N. Lau, L. Roncari, A. Guha, Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens. Neurosurgery 45, 1442-1453 (1999).
15. R. Stupp, W. P. Mason, M. J. van den Bent, M. Weller, B. Fisher, M. J. Taphoorn, K. Belanger, A. A. Brandes, C. Marosi, U. Bogdahn, J. Curschmann, R. C. Janzer, S. K. Ludwin, T. Gorlia, A. Allgeier, D. Lacombe, J. G. Cairncross, E. Eisenhauer, R. O. Mirimanoff, Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987-996 (2005).
16. A. S. Chi, A. D. Norden, P. Y. Wen, Antiangiogenic strategies for treatment of malignant gliomas. Neurotherapeutics 6, 513-526 (2009).
17. J. Verhoeff, O. van Tellingen, A. Claes, L. Stalpers, M. van Linde, D. Richel, W. Leenders, W. van Furth, Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme. BMC Cancer 9, 444 (2009).
18. S. Sathornsumetee, D. A. Reardon, Targeting multiple kinases in glioblastoma multiforme. Expert Opin. Investig. Drugs 18, 277-292 (2009).
19. H. Okada, G. Kohanbash, X. Zhu, E. R. Kastenhuber, A. Hoji, R. Ueda, M. Fujita, Immunotherapeutic approaches for glioma. Crit. Rev. Immunol. 29, 1-42 (2009).
20. M. Fujita, H. Okada, in Brain Tumors - Current and Emerging Therapeutic Strategies, A. L. Abujamra, Ed. (InTech, Rijeka, Croatia, 2011).
21. L. Palma, N. Di Lorenzo, B. Guidetti, Lymphocytic infiltrates in primary glioblastomas and recidivous gliomas. Incidence, fate, and relevance to prognosis in 228 operated cases. J. Neurosurg. 49, 854-861 (1978).
22. W. H. Brooks, W. R. Markesbery, G. D. Gupta, T. L. Roszman, Relationship of lymphocyte invasion and survival of brain tumor patients. Ann. Neurol. 4, 219-224 (1978).
23. A. M. Swartz, Q. J. Li, J. H. Sampson, Rindopepimut: A promising immunotherapeutic for the treatment of glioblastoma multiforme. Immunotherapy 6, 679-690 (2014).
24. S. Dixit, Immunotherapy for high-grade glioma. Future Oncol. 10, 911-915 (2014).
25. G. P. Linette, E. A. Stadtmauer, M. V. Maus, A. P. Rapoport, B. L. Levine, L. Emery, L. Litzky, A. Bagg, B. M. Carreno, P. J. Cimino, G. K. Binder-Scholl, D. P. Smethurst, A. B. Gerry, N. J. Pumphrey, A. D. Bennett, J. E. Brewer, J. Dukes, J. Harper, H. K. Tayton-Martin, B. K. Jakobsen, N. J. Hassan, M. Kalos, C. H. June, Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122, 863-871 (2013).
26. B. J. Cameron, A. B. Gerry, J. Dukes, J. V. Harper, V. Kannan, F. C. Bianchi, F. Grand, J. E. Brewer, M. Gupta, G. Plesa, G. Bossi, A. Vuidepot, A. S. Powlesland, A. Legg, K. J. Adams, A. D. Bennett, N. J. Pumphrey, D. D.Williams, G. Binder-Scholl, I. Kulikovskaya, B. L. Levine, J. L. Riley, A. Varela-Rohena, E. A. Stadtmauer, A. P. Rapoport, G. P. Linette, C. H. June, N. J. Hassan, M. Kalos, B. K. Jakobsen, Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci. Transl. Med. 5, 197ra103 (2013).
27. R. A. Morgan, L. A. Johnson, J. L. Davis, Z. Zheng, K. D. Woolard, E. A. Reap, S. A. Feldman, N. Chinnasamy, C. T. Kuan, H. Song, W. Zhang, H. A. Fine, S. A. Rosenberg, Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Hum. Gene Ther. 23, 1043-1053 (2012).
28. J. H. Sampson, B. D. Choi, L. Sanchez-Perez, C. M. Suryadevara, D. J. Snyder, C. T. Flores, R. J. Schmittling, S. K. Nair, E. A. Reap, P. K. Norberg, J. E. Herndon II, C. T. Kuan, R. A. Morgan, S. A. Rosenberg, L. A. Johnson, EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin. Cancer Res. 20, 972-984 (2014).
29. M. Ohno, T. Ohkuri, A. Kosaka, K. Tanahashi, C. H. June, A. Natsume, H. Okada, Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts. J. Immunother. Cancer 1, 21 (2013).
30. M. V. Maus, A. R. Haas, G. L. Beatty, S. M. Albelda, B. L. Levine, X. Liu, Y. Zhao, M. Kalos, C. H. June, T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol. Res. 1, 26-31 (2013).
31. A. A. Jungbluth, E. Stockert, H. J. Huang, V. P. Collins, K. Coplan, K. Iversen, D. Kolb, T. J. Johns, A. M. Scott, W. J. Gullick, G. Ritter, L. Cohen, M. J. Scanlan, W. K. Cavenee, L. J. Old, A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor. Proc. Natl. Acad. Sci. U.S.A. 100, 639-644 (2003).
32. D. Patel, A. Lahiji, S. Patel, M. Franklin, X. Jimenez, D. J. Hicklin, X. Kang, Monoclonal antibody cetuximab binds to and down-regulates constitutively activated epidermal growth factor receptor vIII on the cell surface. Anticancer Res. 27, 3355-3366 (2007).
33. M. V. Maus, J. A. Fraietta, B. L. Levine, M. Kalos, Y. Zhao, C. H. June, Adoptive immunotherapy for cancer or viruses. Annu. Rev. Immunol. 32, 189-225 (2014).
34. + T-cell responses to vaccine and is required for efficacy against brain tumors in mice. PLOS One 8, e59082 (2013).
35. M. H. Kershaw, J. A. Westwood, L. L. Parker, G. Wang, Z. Eshhar, S. A. Mavroukakis, D. E. White, J. R. Wunderlich, S. Canevari, L. Rogers-Freezer, C. C. Chen, J. C. Yang, S. A. Rosenberg, P. Hwu, A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin. Cancer Res. 12, 6106-6115 (2006).
36. B. G. Till, M. C. Jensen, J. Wang, E. Y. Chen, B. L. Wood, H. A. Greisman, X. Qian, S. E. James, A. Raubitschek, S. J. Forman, A. K. Gopal, J. M. Pagel, C. G. Lindgren, P. D. Greenbergt, S. R. Riddell, O. W. Press, Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 112, 2261-2271 (2008).
37. M. Kalos, B. L. Levine, D. L. Porter, S. Katz, S. A. Grupp, A. Bagg, C. H. June, T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci. Transl. Med. 3, 95ra73 (2011).
38. L. A. Johnson, R. A. Morgan, M. E. Dudley, L. Cassard, J. C. Yang, M. S. Hughes, U. S. Kammula, R. E. Royal, R. M. Sherry, J. R. Wunderlich, C. C. Lee, N. P. Restifo, S. L. Schwarz, A. P. Cogdill, R. J. Bishop, H. Kim, C. C. Brewer, S. F. Rudy, C. VanWaes, J. L. Davis, A. Mathur, R. T. Ripley, D. A. Nathan, C. M. Laurencot, S. A. Rosenberg, Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114, 535-546 (2009).
39. M. R. Parkhurst, J. C. Yang, R. C. Langan, M. E. Dudley, D. A. Nathan, S. A. Feldman, J. L. Davis, R. A. Morgan, M. J. Merino, R. M. Sherry, M. S. Hughes, U. S. Kammula, G. Q. Phan, R. M. Lim, S. A. Wank, N. P. Restifo, P. F. Robbins, C. M. Laurencot, S. A. Rosenberg, T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 19, 620-626 (2011).
40. B. L. Levine, W. B. Bernstein, M. Connors, N. Craighead, T. Lindsten, C. B. Thompson, C. H. June, Effects of CD28 costimulation on long-term proliferation of CD4+ T cells in the absence of exogenous feeder cells. J. Immunol. 159, 5921-5930 (1997).
41. M. C. Milone, J. D. Fish, C. Carpenito, R. G. Carroll, G. K. Binder, D. Teachey, M. Samanta, M. Lakhal, B. Gloss, G. Danet-Desnoyers, D. Campana, J. L. Riley, S. A. Grupp, C. H. June, Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol. Ther. 17, 1453-1464 (2009).
42. J. Couzin-Frankel, Breakthrough of the year 2013. Cancer immunotherapy. Science 342, 1432-1433 (2013).
43. R. J. Brentjens, I. Riviere, J. H. Park, M. L. Davila, X. Wang, J. Stefanski, C. Taylor, R. Yeh, S. Bartido, O. Borquez-Ojeda, M. Olszewska, Y. Bernal, H. Pegram, M. Przybylowski, D. Hollyman, Y. Usachenko, D. Pirraglia, J. Hosey, E. Santos, E. Halton, P. Maslak, D. Scheinberg, J. Jurcic, M. Heaney, G. Heller, M. Frattini, M. Sadelain, Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 118, 4817-4828 (2011).
44. M. L. Davila, I. Riviere, X. Wang, S. Bartido, J. Park, K. Curran, S. S. Chung, J. Stefanski, O. Borquez-Ojeda, M. Olszewska, J. Qu, T. Wasielewska, Q. He, M. Fink, H. Shinglot, M. Youssif, M. Satter, Y. Wang, J. Hosey, H. Quintanilla, E. Halton, Y. Bernal, D. C. Bouhassira, M. E. Arcila, M. Gonen, G. J. Roboz, P. Maslak, D. Douer, M. G. Frattini, S. Giralt, M. Sadelain, R. Brentjens, Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6, 224ra225 (2014).
45. P. F. Robbins, R. A. Morgan, S. A. Feldman, J. C. Yang, R. M. Sherry, M. E. Dudley, J. R. Wunderlich, A. V. Nahvi, L. J. Helman, C. L. Mackall, U. S. Kammula, M. S. Hughes, N. P. Restifo, M. Raffeld, C. C. Lee, C. L. Levy, Y. F. Li, M. El-Gamil, S. L. Schwarz, C. Laurencot, S. A. Rosenberg, Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 29, 917-924 (2011).
46. S. Santoro, S. Kim, G. Motz, D. Alatzoglou, C. Li, M. Irving, D. Powell Jr., G. Coukos, T cells bearing a chimeric antigen receptor against prostate-specific membrane antigen mediate vascular disruption and result in tumor regression. Cancer Immunol. Res. 3, 68-84 (2015).
47. C. U. Louis, B. Savoldo, G. Dotti, M. Pule, E. Yvon, G. D. Myers, C. Rossig, H. V. Russell, O. Diouf, E. Liu, H. Liu, M. F. Wu, A. P. Gee, Z. Mei, C. M. Rooney, H. E. Heslop, M. K. Brenner, Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 118, 6050-6056 (2011).
48. J. H. Sampson, A. B. Heimberger, G. E. Archer, K. D. Aldape, A. H. Friedman, H. S. Friedman, M. R. Gilbert, J. E. Herndon II, R. E. McLendon, D. A.Mitchell, D. A. Reardon, R. Sawaya, R. J. Schmittling, W. Shi, J. J. Vredenburgh, D. D. Bigner, Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J. Clin. Oncol. 28, 4722-4729 (2010).
49. B. Savoldo, C. A. Ramos, E. Liu, M. P. Mims, M. J. Keating, G. Carrum, R. T. Kamble, C. M. Bollard, A. P. Gee, Z. Mei, H. Liu, B. Grilley, C. M. Rooney, H. E. Heslop, M. K. Brenner, G. Dotti, CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J. Clin. Invest. 121, 1822-1826 (2011).
50. W. Haso, D. W. Lee, N. N. Shah, M. Stetler-Stevenson, C. M. Yuan, I. H. Pastan, D. S. Dimitrov, R. A. Morgan, D. J. FitzGerald, D. M. Barrett, A. S. Wayne, C. L. Mackall, R. J. Orentas, Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 121, 1165-1174 (2013).
51. A. Pandita, K. D. Aldape, G. Zadeh, A. Guha, C. D. James, Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR. Genes Chromosomes Cancer 39, 29-36 (2004).
52. A. Schulte, H. S. Gunther, T. Martens, S. Zapf, S. Riethdorf, C. Wulfing, M. Stoupiec, M. Westphal, K. Lamszus, Glioblastoma stem-like cell lines with either maintenance or loss of high-level EGFR amplification, generated via modulation of ligand concentration. Clin. Cancer Res. 18, 1901-1913 (2012).
53. C. Carpenito, M. C. Milone, R. Hassan, J. C. Simonet, M. Lakhal, M. M. Suhoski, A. Varela-Rohena, K.M. Haines, D. F. Heitjan, S. M. Albelda, R. G. Carroll, J. L. Riley, I. Pastan, C. H. June, Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc. Natl. Acad. Sci. U.S.A. 106, 3360-3365 (2009).