New strategies in engineering T-cell receptor gene-modified T cells to more effectively target malignancies

Clinical Cancer Research

Volumn 21, Issue 23, 2015, Pages 5191-5197

  Schmitt, Thomas M ^a   Stromnes, Ingunn M ^a,b   Chapuis, Aude G ^a   Greenberg, Philip D ^a,b,c  

^a Fred Hutchinson Cancer Research Center   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

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

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; CANCER VACCINE; EPITOPE; T LYMPHOCYTE RECEPTOR; HYBRID PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR; TUMOR ANTIGEN;

ADOPTIVE TRANSFER; ARTICLE; CANCER CELL; CANCER GENE THERAPY; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CD4+ T LYMPHOCYTE; CELL COUNT; CELL MATURATION; CELL SIZE; CELL THERAPY; DISEASE ERADICATION; DNA MODIFICATION; DRUG TREATMENT FAILURE; GENE VECTOR; GENETIC ENGINEERING; HUMAN; IMMUNOLOGICAL TOLERANCE; IN VIVO STUDY; LYMPHOCYTE FUNCTION; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; RECEPTOR AFFINITY; T LYMPHOCYTE; T LYMPHOCYTE RECEPTOR GENE; TARGET CELL DESTRUCTION; TREATMENT RESPONSE; TUMOR ESCAPE; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; ADOPTIVE IMMUNOTHERAPY; ADVERSE EFFECTS; ANIMAL; GENE THERAPY; GENETIC TRANSDUCTION; GENETICS; IMMUNOLOGY; METABOLISM; NEOPLASMS; PROCEDURES; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; ANTIGENS, NEOPLASM; GENETIC THERAPY; GENETIC VECTORS; HUMANS; IMMUNOTHERAPY, ADOPTIVE; NEOPLASMS; RECEPTORS, ANTIGEN, T-CELL; RECOMBINANT FUSION PROTEINS; T-CELL ANTIGEN RECEPTOR SPECIFICITY; T-LYMPHOCYTE SUBSETS; TRANSDUCTION, GENETIC;

EID: 84954126580     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-0860     Document Type: Article

References (79)

1. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 2011;17:4550-7.
2. Dudley M, Yang J, Sherry R, Hughes M, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 2008; 26:5233-9.
3. Chapuis AG, Thompson JA, Margolin KA, Rodmyre R, Lai IP, Dowdy K, et al. Transferred melanoma-specific CD8+ T cells persist, mediate tumor regression, and acquire central memory phenotype. Proc Natl Acad Sci U S A 2012;109:4592-7.
4. De Visser K, Schumacher T, Kruisbeek A. CD8+ T cell tolerance and cancer immunotherapy. J Immunother 2003;26:1-11.
5. Robbins PF, Dudley ME, Wunderlich J, El-Gamil M, Li YF, Zhou J, et al. Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol 2004;173:7125-30.
6. Chapuis AG, Ragnarsson GB, Nguyen HN, Chaney CN, Pufnock JS, Schmitt TM, et al. Transferred WT1-reactive CD8+T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transl Med 2013; 5:174ra27.
7. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Ann Rev Immunol 2004;22:329-60.
8. Thomas DA, Massague J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion ofimmune surveillance. Cancer Cell 2005;8:369-80.
9. Stromnes IM, Schmitt TM, Chapuis AG, Hingorani SR, Greenberg PD. Readapting T cells for cancer therapy: from mouse models to clinical trials. Immunol Rev 2013;257:145-64.
10. Schmitt TM, Ragnarsson GB, Greenberg PD. T cell receptor gene therapy for cancer. Hum Gene Ther 2009;20:1240-8.
11. Berger C, Jensen M, Lansdorp P, Gough M, Elliott C, Riddell S. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest 2008; 118:294-305.
12. Hinrichs CS, Borman ZA, Cassard L, Gattinoni L, Spolski R, Yu Z, et al. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci U S A 2009;106:17469-74.
13. Wucherpfennig KW, Gagnon E, Call MJ, Huseby ES, Call ME. Structural biology of the T-cell receptor: insights into receptor assembly, ligand recognition, and initiation of signaling. Cold Spring Harb Perspect Biol 2010;2:a005140.
14. Heemskerk M, Hagedoorn R, van der Hoorn M, van der Veken L, Hoogeboom M, Kester M, et al. Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex. Blood 2007;109: 235-43.
15. van Loenen MM, de Boer R, Amir AL, Hagedoorn RS, Volbeda GL, Willemze R, et al. Mixed T cell receptor dimers harbor potentially harmful neoreactivity. Proc Natl Acad Sci U S A 2010;107:10972-7.
16. Cohen C, Li Y, El-Gamil M, Robbins P, Rosenberg S, Morgan R. Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res 2007;67:3898-903.
17. Kuball J, Dossett M, Wolfl M, Ho W, Voss R-H, Fowler C, et al. Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 2007;109:2331-8.
18. Voss R, Willemsen R, Kuball J, Grabowski M, Engel R, Intan R, et al. Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells. J Immunol 2008;180: 391-401.
19. Yang S, Cohen C, Peng P, Zhao Y, Cassard L, Yu Z, et al. Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition. Gene Ther 2008;15: 1411-23.
20. Provasi E, Genovese P, Lombardo A, Magnani Z, Liu PQ, Reik A, et al. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med 2012;18:807-15.
21. Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, et al. Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res 2009;69:9003-11.
22. Sinn P, Sauter S, McCray P. Gene therapy progress and prospects: development of improved lentiviral and retroviral vectors-design, biosafety, and production. Gene Ther 2005;12:1089-98.
23. Izsvák Z, Hackett PB, Cooper LJN, Ivics Z. Translating Sleeping Beauty transposition into cellular therapies: victories and challenges. Bioessays 2010;32:756-67.
24. Klebanoff CA, Gattinoni L, Palmer DC, Muranski P, Ji Y, Hinrichs CS, et al. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice. Clin Cancer Res 2011; 17:5343-52.
25. West EE, Youngblood B, Tan WG, Jin H-T, Araki K, Alexe G, et al. Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load. Immunity 2011;35:285-98.
26. Krogsgaard M, Davis MM. How T cells "see" antigen. Nat Immunol 2005; 6:239-45.
27. Xue S-A, Gao L, Thomas S, Hart DP, Xue JZ, Gillmore R, et al. Development of a Wilms' tumor antigen-specific T-cell receptor for clinical trials: engineered patient's T cells can eliminate autologous leukemia blasts in NOD/SCID mice. Haematologica 2010;95:126-34.
28. Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res 2009;15:5323-37.
29. Schmitt TM, Aggen DH, Stromnes IM, Dossett ML, Richman SA, Kranz DM, et al. Enhanced-affinity murine T-cell receptors for tumor/self-antigens can be safe in gene therapy despite surpassing the threshold for thymic selection. Blood 2013;122:348-56.
30. Shusta E, Holler P, Kieke M, Kranz D, Wittrup K. Directed evolution of a stable scaffold for T-cell receptor engineering. Nat Biotechnol 2000; 18:754-9.
31. Richman S, Kranz D. Display, engineering, and applications of antigenspecific T cell receptors. Biomol Eng 2007;24:361-73.
32. Zhong S, Malecek K, Johnson LA, Yu Z, Vega-Saenz de Miera E, Darvishian F, et al. T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy. Proc Natl Acad Sci U S A 2013;110:6973-8.
33. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L, et al. Cardiovascular toxicity and titin cross-reactivity of affinityenhanced T cells in myeloma and melanoma. Blood 2013;122: 863-71.
34. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NYESO-1. J Clin Oncol 2011;29:917-24.
35. Chinnasamy N, Wargo JA, Yu Z, Rao M, Frankel TL, Riley JP, et al. A TCR Targeting the HLA-A∗0201-restricted epitope of MAGE-A3 recognizes multiple epitopes of the MAGE-A antigen superfamily in several types of cancer. J Immunol 2011;186:685-96.
36. Obenaus M, Leitão C, Leisegang M, Chen X, Gavvovidis I, van der Bruggen P, et al. Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice. Nat Biotechnol 2015;33:402-7.
37. Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, et al. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 2013;36:133-51.
38. Stone JD, Kranz DM. Role of T cell receptor affinity in the efficacy and specificity of adoptive T cell therapies. Front Immunol 2013;4:244.
39. Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and Genetic Properties of tumors associated with local immune cytolytic activity. Cell 2015;160:48-61.
40. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LAJ, Kinzler KW. Cancer genome landscapes. Science 2013;339:1546-58.
41. Chu NJ, Armstrong TD, Jaffee EM. Nonviral oncogenic antigens and the inflammatory signals driving early cancer development as targets for cancer immunoprevention. Clin Cancer Res 2015;21:1549-57.
42. Popović J, Li L-P, Kloetzel PM, Leisegang M, Uckert W, Blankenstein T. The only proposed T-cell epitope derived from the TEL-AML1 translocation is not naturally processed. Blood 2011;118:946-54.
43. Blankenstein T, Leisegang M, Uckert W, Schreiber H. Targeting cancerspecific mutations by T cell receptor gene therapy. Curr Opin Immunol 2015;33:112-9.
44. Castle JC, Kreiter S, Diekmann J, Löwer M, van de Roemer N, de Graaf J, et al. Exploiting the mutanome for tumor vaccination. Cancer Res 2012;72:1081-91.
45. Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, Magrini VJ, et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 2012;482:400-4.
46. van Rooij N, van Buuren MM, Philips D, Velds A, Toebes M, Heemskerk B, et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol 2013;31: e439-42.
47. Robbins PF, Lu Y-C, El-Gamil M, Li YF, Gross C, Gartner J, et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med 2013;19: 747-52.
48. Linnemann C, van Buuren MM, Bies L, Verdegaal EME, Schotte R, Calis JJA, et al. High-throughput epitope discovery reveals frequent recognition of neo-antigens byCD4+T cells inhumanmelanoma. Nat Med 2015;21:81-5.
49. Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E, et al. PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltratinghuman tumors. J Clin Invest 2014;124:2246-59.
50. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Mutational landscape determines sensitivity to PD-1 blockade in nonsmall cell lung cancer. Science 2015;348:124-8.
51. Fritsch EF, Hacohen N, Wu CJ. Personal neoantigen cancer vaccines: The momentum builds. Oncoimmunology 2014;3:e29311.
52. Leen AM, Bollard CM, Mendizabal AM, Shpall EJ, Szabolcs P, Antin JH, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 2013;121:5113-23.
53. Torikai H, Reik A, Soldner F, Warren EH, Yuen C, Zhou Y, et al. Toward eliminating HLA class I expression to generate universal cells from allogeneic donors. Blood 2013;122:1341-9.
54. Greenberg PD, Kern DE, Cheever MA. Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+,2-T cells. Tumor eradication does not require participation of cytotoxic T cells. J Exp Med 1985;161:1122-34.
55. Greenberg PD, Cheever MA, Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2-lymphocytes. J Exp Med 1981;154:952-63.
56. Perez-Diez A, Joncker NT, Choi K, Chan WF, Anderson CC, Lantz O, et al. CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood 2007;109:5346-54.
57. Xie Y, Akpinarli A, Maris C, Hipkiss EL, Lane M, Kwon E-KM, et al. Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma. J Exp Med 2010;207:651-67.
58. Schietinger A, Philip M, Liu RB, Schreiber K, Schreiber H. Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase. J Exp Med 2010;207:2469-77.
59. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4(+) T cells in the antitumor immune response. J Exp Med 1998;188:2357-68.
60. Nishimura T, Iwakabe K, Sekimoto M, Ohmi Y, Yahata T, Nakui M, et al. Distinct role of antigen-specific T helper type 1 (Th1) and Th2 cells in tumor eradication in vivo. J Exp Med 1999;190:617-27.
61. Yasukawa M, Ohminami H, Arai J, Kasahara Y, Ishida Y, Fujita S. Granule exocytosis, and not the Fas/Fas ligand system, is the main pathway of cytotoxicity mediated by alloantigen-specific CD4+ as well as CD8+ cytotoxic T lymphocytes in humans. Blood 2000;95: 2352-5.
62. Hombach A, Köhler H, Rappl G, Abken H. Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor. J Immunol 2006; 177:5668-75.
63. Kim H-J, Cantor H. CD4 T-cell subsets and tumor immunity: the helpful and the not-so-helpful. Cancer Immunol Res 2014;2:91-8.
64. Adusumilli PS, Cherkassky L, Villena-Vargas J, Colovos C, Servais E, Plotkin J, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med 2014;6:261ra151-1.
65. Hunder NN, Wallen H, Cao J, Hendricks DW, Reilly JZ, Rodmyre R, et al. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med 2008;358:2698-703.
66. Soto CM, Stone JD, Chervin AS, Engels B, Schreiber H, Roy EJ, et al. MHCclass I-restricted CD4 T cells: a nanomolar affinity TCR has improved antitumor efficacy in vivo compared to themicromolar wild-type TCR. Cancer Immunol Immunother 2013;62:359-69.
67. Engels B, Chervin AS, Sant AJ, Kranz DM, Schreiber H. Long-term persistence of CD4(+) but rapid disappearance of CD8(+) T cells expressing an MHC class I-restricted TCR of nanomolar affinity. Mol Ther 2012; 20:652-60.
68. Ghorashian S, Veliça P, Chua I, McNicol A-M, Carpenter B, Holler A, et al. CD8 T cell tolerance to a tumor-associated self-antigen is reversed by CD4 T cells engineered to express the same T cell receptor. J Immunol 2015; 194:1080-9.
69. Kessels HWHG, Kessels HWHG, Schepers K, van den Boom MD, van den Boom MD, Topham DJ, et al. Generation of T cell help through aMHCclass I-restricted TCR. J Immunol 2006;177:976-82.
70. Wherry EJ. T cell exhaustion. Nat Immunol 2011;12:492-9.
71. Jiang Y, Li Y, Zhu B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis 2015;6:e1792.
72. Stephan MT, Ponomarev V, Brentjens RJ, Chang AH, Dobrenkov KV, Heller G, et al. T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nat Med 2007;13:1440-9.
73. Ankri C, Shamalov K, Horovitz-Fried M, Mauer S, Cohen CJ. Human T cells engineered to express a programmed death 1/28 costimulatory retargeting molecule display enhanced antitumor activity. J Immunol 2013;191: 4121-9.
74. Leen AM, Sukumaran S, Watanabe N, Mohammed S, Keirnan J, Yanagisawa R, et al. Reversal of tumor immune inhibition using a chimeric cytokine receptor. Mol Ther 2014;22:1211-20.
75. Stromnes IM, Blattman JN, Tan X, Jeevanjee S, Gu H, Greenberg PD. Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice. J Clin Invest 2010;120: 3722-34.
76. Stromnes IM, Fowler C, Casamina CC, Georgopolos CM, McAfee MS, Schmitt TM, et al. Abrogation of SRC homology region 2 domaincontaining phosphatase 1 in tumor-specific T cells improves efficacy of adoptive immunotherapy by enhancing the effector function and accumulation of short-lived effector T cells in vivo. J Immunol 2012;189: 1812-25.
77. Chou CK, Schietinger A, Liggitt HD, Tan X, Funk S, Freeman GJ, et al. Cellintrinsic abrogation of TGF-beta signaling delays but does not prevent dysfunction of self/tumor-specific CD8 T cells in a murine model of autochthonous prostate cancer. J Immunol 2012;189:3936-46.
78. Zhang L, Kerkar SP, Yu Z, Zheng Z, Yang S, Restifo NP, et al. Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol Ther 2011;19:751-9.
79. Crespo J, Sun H, Welling TH, Tian Z, Zou W. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment. Curr Opin Immunol 2013;25:214-21.