PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses

Science Translational Medicine

Volumn 5, Issue 215, 2013, Pages

  Fedorov, Victor D ^a,b   Themeli, Maria ^a   Sadelain, Michel ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; PROGRAMMED DEATH 1 RECEPTOR; T LYMPHOCYTE RECEPTOR;

ANIMAL EXPERIMENT; ANTIGEN RECOGNITION; ARTICLE; CELL FATE; CELL SPECIFICITY; CELL SURFACE; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOTOXIC T LYMPHOCYTE; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOREGULATION; IMMUNOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; STOICHIOMETRY; T LYMPHOCYTE ACTIVATION;

ANIMALS; CELL LINE; CELL PROLIFERATION; CTLA-4 ANTIGEN; CYTOKINES; DENDRITIC CELLS; FIBROBLASTS; HUMANS; IMMUNOSUPPRESSION; IMMUNOTHERAPY; LUMINESCENCE; LYMPHOCYTES; MALE; MICE; MICE, INBRED NOD; MICE, SCID; NIH 3T3 CELLS; PROGRAMMED CELL DEATH 1 RECEPTOR; PROTEOMICS; RECEPTORS, ANTIGEN; T-LYMPHOCYTES;

EID: 84891708419     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3006597     Document Type: Article

References (56)

1. J. N. Blattman, P. D. Greenberg, Cancer immunotherapy: A treatment for the masses. Science 305, 200-205 (2004).
2. N. P. Restifo, M. E. Dudley, S. A. Rosenberg, Adoptive immunotherapy for cancer: Harnessing the T cell response. Nat. Rev. Immunol. 12, 269-281 (2012).
3. M. Sadelain, R. Brentjens, I. Rivière, The promise and potential pitfalls of chimeric antigen receptors. Curr. Opin. Immunol. 21, 215-223 (2009).
4. C. J. Turtle, M. Hudecek, M. C. Jensen, S. R. Riddell, Engineered T cells for anti-cancer therapy. Curr. Opin. Immunol. 24, 633-639 (2012).
5. B. R. Blazar, W. J. Murphy, M. Abedi, Advances in graft-versus-host disease biology and therapy. Nat. Rev. Immunol. 12, 443-458 (2012).
6. T. M. Brusko, A. L. Putnam, J. A. Bluestone, Human regulatory T cells: Role in autoimmune disease and therapeutic opportunities. Immunol. Rev. 223, 371-390 (2008).
7. 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).
8. R. J. Brentjens, I. Rivière, 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).
9. R. J. Brentjens, M. L. Davila, I. Riviere, J. Park, X. Wang, L. G. Cowell, S. Bartido, J. Stefanski, C. Taylor, M. Olszewska, O. Borquez-Ojeda, J. Qu, T. Wasielewska, Q. He, Y. Bernal, I. V. Rijo, C. Hedvat, R. Kobos, K. Curran, P. Steinherz, J. Jurcic, T. Rosenblat, P. Maslak, M. Frattini, M. Sadelain, CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl. Med. 5, 177ra38 (2013).
10. 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).
11. 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).
12. 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).
13. 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).
14. J. L. Ferrara, J. E. Levine, P. Reddy, E. Holler, Graft-versus-host disease. Lancet 373, 1550-1561 (2009).
15. E. Kotsiou, J. K. Davies, New ways to separate graft-versus-host disease and graft-versus-tumour effects after allogeneic haematopoietic stem cell transplantation. Br. J. Haematol. 160, 133-145 (2013).
16. G. Akpek, S. M. Lee, V. Anders, G. B. Vogelsang, A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease. Biol. Blood Marrow Transplant. 7, 495-502 (2001).
17. M. T. Lupo-Stanghellini, E. Provasi, A. Bondanza, F. Ciceri, C. Bordignon, C. Bonini, Clinical impact of suicide gene therapy in allogeneic hematopoietic stem cell transplantation. Hum. Gene Ther. 21, 241-250 (2010).
18. A. Di Stasi, S. K. Tey, G. Dotti, Y. Fujita, A. Kennedy-Nasser, C. Martinez, K. Straathof, E. Liu, A. G. Durett, B. Grilley, H. Liu, C. R. Cruz, B. Savoldo, A. P. Gee, J. Schindler, R. A. Krance, H. E. Heslop, D. M. Spencer, C. M. Rooney, M. K. Brenner, Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365, 1673-1683 (2011).
19. I. Vogler, S. Newrzela, S. Hartmann, N. Schneider, D. von Laer, U. Koehl,M. Grez, An improved bicistronic CD20/tCD34 vector for efficient purification and in vivo depletion of gene-modified T cells for adoptive immunotherapy. Mol. Ther. 18, 1330-1338 (2010).
20. E. Kieback, J. Charo, D. Sommermeyer, T. Blankenstein, W. Uckert, A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer. Proc. Natl. Acad. Sci. U.S.A. 105, 623-628 (2008).
21. D. M. Pardoll, The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252-264 (2012).
22. P. Sharma, K. Wagner, J. D. Wolchok, J. P. Allison, Novel cancer immunotherapy agents with survival benefit: Recent successes and next steps. Nat. Rev. Cancer 11, 805-812 (2011).
23. E. A. Tivol, F. Borriello, A. N. Schweitzer, W. P. Lynch, J. A. Bluestone, A. H. Sharpe, Loss of CTLA-4 leads to massive lymphoproliferation and fatalmultiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3, 541-547 (1995).
24. H. Nishimura, M. Nose, H. Hiai, N. Minato, T. Honjo, Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11, 141-151 (1999).
25. -/- mice as an efficient animal model of type I diabetes. Proc. Natl. Acad. Sci. U.S.A. 102, 11823-11828 (2005).
26. R. V. Parry, J. M. Chemnitz, K. A. Frauwirth, A. R. Lanfranco, I. Braunstein, S. V. Kobayashi, P. S. Linsley, C. B. Thompson, J. L. Riley, CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell. Biol. 25, 9543-9553 (2005).
27. 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).
28. 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. Lebbé, 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).
29. + T-cell memory formation, function, and maintenance. Proc. Natl. Acad. Sci. U.S.A. 108, 266-271 (2011).
30. V. Velu, K. Titanji, B. Zhu, S. Husain, A. Pladevega, L. Lai, T. H. Vanderford, L. Chennareddi, G. Silvestri, G. J. Freeman, R. Ahmed, R. R. Amara, Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature 458, 206-210 (2009).
31. T. P. Gade, W. Hassen, E. Santos, G. Gunset, A. Saudemont, M. C. Gong, R. Brentjens, X. S. Zhong, M. Stephan, J. Stefanski, C. Lyddane, J. R. Osborne, I. M. Buchanan, S. J. Hall, W. D. Heston, I. Rivière, S. M. Larson, J. A. Koutcher, M. Sadelain, Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Cancer Res. 65, 9080-9088 (2005).
32. M. Sadelain, R. Brentjens, I. Rivière, The basic principles of chimeric antigen receptor design. Cancer Discov. 3, 388-398 (2013).
33. Y. Kinoshita, K. Kuratsukuri, S. Landas, K. Imaida, P. M. Rovito Jr., C. Y. Wang, G. P. Haas, Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J. Surg. 30, 628-636 (2006).
34. J. Maher, R. J. Brentjens, G. Gunset, I. Rivière, M. Sadelain, Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRz/CD28 receptor. Nat. Biotechnol. 20, 70-75 (2002).
35. W. A. Teft, M. G. Kirchhof, J. Madrenas, A molecular perspective of CTLA-4 function. Annu. Rev. Immunol. 24, 65-97 (2006).
36. X. Fu, L. Tao, A. Rivera, S. Williamson, X. T. Song, N. Ahmed, X. Zhang, A simple and sensitive method for measuring tumor-specific T cell cytotoxicity. PLOS One 5, e11867 (2010).
37. R. J. Brentjens, E. Santos, Y. Nikhamin, R. Yeh, M. Matsushita, K. La Perle, A. Quintás-Cardama, S. M. Larson, M. Sadelain, Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin. Cancer Res. 13, 5426-5435 (2007).
38. J. C. Markley, M. Sadelain, IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice. Blood 115, 3508-3519 (2010).
39. J. M. Chemnitz, R. V. Parry, K. E. Nichols, C. H. June, J. L. Riley, SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol. 173, 945-954 (2004).
40. T. Yokosuka, M. Takamatsu, W. Kobayashi-Imanishi, A. Hashimoto-Tane, M. Azuma, T. Saito, Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J. Exp. Med. 209, 1201-1217 (2012).
41. Y. T. Bryceson, E. O. Long, Line of attack: NK cell specificity and integration of signals. Curr. Opin. Immunol. 20, 344-352 (2008).
42. S. Amarnath, C. W. Mangus, J. C. Wang, F. Wei, A. He, V. Kapoor, J. E. Foley, P. R. Massey, T. C. Felizardo, J. L. Riley, B. L. Levine, C. H. June, J. A. Medin, D. H. Fowler, The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci. Transl. Med. 3, 111ra120 (2011). Downloaded from stm.sciencemag.org on December 28, 2013
43. K. S. Peggs, S. A. Quezada, J. P. Allison, Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy. Immunol. Rev. 224, 141-165 (2008).
44. C. E. Rudd, The reverse stop-signal model for CTLA4 function. Nat. Rev. Immunol. 8, 153-160 (2008).
45. M. Uhlen, P. Oksvold, L. Fagerberg, E. Lundberg, K. Jonasson, M. Forsberg, M. Zwahlen, C. Kampf, K. Wester, S. Hober, H. Wernerus, L. Björling, F. Ponten, Towards a knowledge-based Human Protein Atlas. Nat. Biotechnol. 28, 1248-1250 (2010).
46. M. Campoli, S. Ferrone, HLA antigen changes in malignant cells: Epigenetic mechanisms and biologic significance. Oncogene 27, 5869-5885 (2008).
47. Y. Cui, Y. Ying, A. van Hasselt, K. M. Ng, J. Yu, Q. Zhang, J. Jin, D. Liu, J. S. Rhim, S. Y. Rha, M. Loyo, A. T. Chan, G. Srivastava, G. S. Tsao, G. C. Sellar, J. J. Sung, D. Sidransky, Q. Tao, OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. PLOS One 3, e2990 (2008).
48. K. Singh, D. Mogare, R. O. Giridharagopalan, R. Gogiraju, G. Pande, S. Chattopadhyay, p53 target gene SMAR1 is dysregulated in breast cancer: Its role in cancer cell migration and invasion. PLOS One 2, e660 (2007).
49. L. Meimei, L. Peiling, L. Baoxin, L. Changmin, Z. Rujin, H. Chunjie, Lost expression of DCC gene in ovarian cancer and its inhibition in ovarian cancer cells. Med. Oncol. 28, 282-289 (2011).
50. S. Tsuboi, S. Hatakeyama, C. Ohyama, M. Fukuda, Two opposing roles of O-glycans in tumor metastasis. Trends Mol. Med. 18, 224-232 (2012).
51. B. Tsuchiya, Y. Sato, T. Kameya, I. Okayasu, K. Mukai, Differential expression of N-cadherin and E-cadherin in normal human tissues. Arch. Histol. Cytol. 69, 135-145 (2006).
52. C. L. Chaffer, R. A. Weinberg, A perspective on cancer cellmetastasis. Science 331, 1559-1564 (2011).
53. M. T. Stephan, V. Ponomarev, R. J. Brentjens, A. H. Chang, K. V. Dobrenkov, G. Heller, M. Sadelain, T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nat. Med. 13, 1440-1449 (2007).
54. D. N. Burshtyn, C. Davidson, Natural killer cell conjugate assay using two-color flow cytometry. Methods Mol. Biol. 612, 89-96 (2010).
55. M. Themeli, C. C. Kloss, G. Ciriello, V. D. Fedorov, F. Perna, M. Gonen, M. Sadelain, Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nat. Biotechnol. 31, 928-933 (2013).
56. + cytolytic T lymphocyte responses. J. Immunol. 174, 758-766 (2005).