Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting

Clinical Cancer Research

Volumn 23, Issue 10, 2017, Pages 2478-2490

  Slaney, Clare Y ^a,b   Von Scheidt, Bianca ^a,b   Davenport, Alexander J ^a,b   Beavis, Paul A ^a,b   Westwood, Jennifer A ^a,b   Mardiana, Sherly ^a,b   Tscharke, David C ^c   Ellis, Sarah ^a,b   Prince, H Miles ^a,b   Trapani, Joseph A ^a,b   Johnstone, Ricky W ^a,b   Smyth, Mark J ^d   Teng, Michele W ^d   Ali, Aesha ^a,b   Yu, Zhiya ^e   Rosenberg, Steven A ^e   Restifo, Nicholas P ^e   Neeson, Paul ^a,b   Darcy, Phillip K ^a,b,f   Kershaw, Michael H ^a,b,f  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c Biology and Environment   (Australia)

^d QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^e NATIONAL CANCER INSTITUTE   (United States)

^f MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; CHEMOKINE RECEPTOR CXCR3; CHIMERIC ANTIGEN RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GAMMA INTERFERON; GLYCOPROTEIN GP 100; RECOMBINANT INTERLEUKIN 2; T LYMPHOCYTE RECEPTOR; CANCER VACCINE; ERBB2 PROTEIN, HUMAN; LYMPHOCYTE ANTIGEN RECEPTOR; MELANOCYTE PROTEIN PMEL 17;

ADOPTIVE TRANSFER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BREAST TUMOR; CANCER IMMUNIZATION; CANCER INHIBITION; CANCER SURVIVOR; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELL INFILTRATION; CEREBELLUM; CONTROLLED STUDY; DISEASE CLEARANCE; DRUG DOSE TITRATION; DRUG MEGADOSE; FEMALE; IMMUNOLOGICAL MEMORY; LIVER TUMOR; LYMPHOCYTE PROLIFERATION; LYMPHOCYTE TRANSFER; MOUSE; NEUROTOXICITY; NONHUMAN; PRIORITY JOURNAL; SOLID MALIGNANT NEOPLASM; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TUMOR CELL DESTRUCTION; TUMOR REGRESSION; TUMOR VOLUME; VACCINIA VIRUS; VIRUS RECOMBINANT; ADOPTIVE IMMUNOTHERAPY; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN TUMOR; CELL PROLIFERATION; DRUG EFFECTS; FLOW CYTOMETRY; GENETICS; HUMAN; IMMUNOLOGY; PATHOLOGY; REMISSION; TRANSGENIC MOUSE; TUMOR CELL LINE;

ANIMALS; AUTOANTIGENS; BRAIN NEOPLASMS; BREAST NEOPLASMS; CANCER VACCINES; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TUMOR; CELL PROLIFERATION; FEMALE; FLOW CYTOMETRY; GP100 MELANOMA ANTIGEN; HUMANS; IMMUNOTHERAPY, ADOPTIVE; INTERFERON-GAMMA; MICE; MICE, TRANSGENIC; RECEPTOR, ERBB-2; RECEPTORS, ANTIGEN, T-CELL; REMISSION INDUCTION; VACCINIA VIRUS;

EID: 85020434429     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-16-1860     Document Type: Article

References (64)

1. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 2012;12:269-81.
2. Hinrichs CS, Rosenberg SA. Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol Rev 2014;257:56-71.
3. Ellebaek E, Iversen TZ, Junker N, Donia M, Engell-Noerregaard L, Met O, et al. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. J Transl Med 2012;10:169.
4. Itzhaki O, Hovav E, Ziporen Y, Levy D, Kubi A, Zikich D, et al. Establishment and large-scale expansion of minimally cultured "young" tumor infiltrating lymphocytes for adoptive transfer therapy. J Immunother 2011;34:212-20.
5. Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res 2012;18:6758-70.
6. Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 2010;115:925-35.
7. Yannelli JR, Hyatt C, McConnell S, Hines K, Jacknin L, Parker L, et al. Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience. Int J Cancer 1996;65:413-21.
8. Kershaw MH, Westwood JA, Darcy PK. Gene-engineered T cells for cancer therapy. Nat Rev Cancer 2013;13:525-41.
9. Kershaw MH, Teng MW, Smyth MJ, Darcy PK. Supernatural T cells: genetic modification of T cells for cancer therapy. Nat Rev Immunol 2005;5:928-40.
10. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014;6:224ra25.
11. Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, 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;33:540-9.
12. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, 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;385:517-28.
13. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014;371:1507-17.
14. 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.
15. Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci U S A 2009;106:3360-5.
16. Posey ADJr, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, et al. Engineered CAR T cells targeting the cancer-associated Tn-Glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity 2016;44:1444-54.
17. Wang LX, Westwood JA, Moeller M, Duong CP, Wei WZ, Malaterre J, et al. Tumor ablation by gene-modified T cells in the absence of autoimmunity. Cancer Res 2010;70:9591-8.
18. Chmielewski M, Hahn O, Rappl G, Nowak M, Schmidt-Wolf IH, Hombach AA, et al. T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice. Gastroenterology 2012;143:1095-107.
19. John LB, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM, et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 2013;19:5636-46.
20. Kershaw MH, Westwood JA, Hwu P. Dual-specific T cells combine proliferation and antitumor activity. Nat Biotechnol 2002;20:1221-7.
21. Murphy A, Westwood JA, Brown LE, Teng MW, Moeller M, Xu Y, et al. Antitumor activity of dual-specific T cells and influenza virus. Cancer Gene Ther 2007;14:499-508.
22. Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 2006;12:6106-15.
23. Wen FT, Thisted RA, Rowley DA, Schreiber H. A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth. Oncoimmunology 2012;1:172-8.
24. Overwijk WW, Theoret MR, Finkelstein SE, Surman DR, de Jong LA, Vyth- Dreese FA, et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J Exp Med 2003;198:569-80.
25. Yong CS, Westwood JA, Schroder J, Papenfuss AT, von Scheidt B, Moeller M, et al. Expression of a chimeric antigen receptor in multiple leukocyte lineages in transgenic mice. PLoS One 2015;10:e0140543.
26. Piechocki MP, Ho YS, Pilon S, Wei WZ. Human ErbB-2 (Her-2) transgenic mice: a model system for testing Her-2 based vaccines. J Immunol 2003;171:5787-94.
27. Johnstone CN, Smith YE, Cao Y, Burrows AD, Cross RS, Ling X, et al. Functional and molecular characterisation of EO771.LMB tumours, a new C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer. Dis Model Mech 2015;8:237-51.
28. Shiloni E, Karp SE, Custer MC, Shilyansky J, Restifo NP, Rosenberg SA, et al. Retroviral transduction of interferon-gamma cDNA into a nonimmunogenic murine fibrosarcoma: generation of T cells in draining lymph nodes capable of treating established parental metastatic tumor. Cancer Immunol Immunother 1993;37:286-92.
29. Corbett TH, Griswold DPJr, Roberts BJ, Peckham JC, Schabel FM Jr. Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res 1975;35:2434-9.
30. Moeller M, Haynes NM, Trapani JA, Teng MW, Jackson JT, Tanner JE, et al. A functional role for CD28 costimulation in tumor recognition by single-chain receptor-modified T cells. Cancer Gene Ther 2004;11:371-9.
31. Overwijk WW, Tsung A, Irvine KR, Parkhurst MR, Goletz TJ, Tsung K, et al. gp100/pmel 17 is a murine tumor rejection antigen: induction of "self"-reactive, tumoricidal T cells using high-affinity, altered peptide ligand. J Exp Med 1998;188:277-86.
32. Lev A, Takeda K, Zanker D, Maynard JC, Dimberu P, Waffarn E, et al. The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation. Immunity 2008;28:787-98.
33. Restifo NP, Bacik I, Irvine KR, Yewdell JW, McCabe BJ, Anderson RW, et al. Antigen processing in vivo and the elicitation of primary CTL responses. J Immunol 1995;154:4414-22.
34. Earl PL, Moss B, Wyatt LS, Carroll MW. Generation of recombinant vaccinia viruses. Curr Protoc Protein Sci 2001;Chapter 5:Unit 5.13.
35. Amos SM, Pegram HJ, Westwood JA, John LB, Devaud C, Clarke CJ, et al. Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice. Cancer Immunol Immunother 2011;60:671-83.
36. Yong CS, Sharkey J, Duscio B, Venville B, Wei WZ, Jones RF, et al. Embryonic lethality in homozygous human Her-2 transgenic mice due to disruption of the Pds5b gene. PLoS One 2015;10:e0136817.
37. Kalaitsidou M, Kueberuwa G, Schutt A, Gilham DE. CAR T-cell therapy: toxicity and the relevance of preclinical models. Immunotherapy 2015;7:487-97.
38. van der Stegen SJ, Davies DM, Wilkie S, Foster J, Sosabowski JK, Burnet J, et al. Preclinical in vivo modeling of cytokine release syndrome induced by ErbB-retargeted human T cells: identifying a window of therapeutic opportunity? J Immunol 2013;191:4589-98.
39. Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, et al. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res 2015;75:296-305.
40. Forget MA, Huon Y, Reuben A, Grange C, Liberman M, Martin J, et al. Stimulation of Wnt/ss-catenin pathway in human CD8+ T lymphocytes from blood and lung tumors leads to a shared young/memory phenotype. PLoS One 2012;7:e41074.
41. 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.
42. Uno T, Takeda K, Kojima Y, Yoshizawa H, Akiba H, Mittler RS, et al. Eradication of established tumors in mice by a combination antibody-based therapy. Nat Med 2006;12:693-8.
43. Wang B, Norbury CC, Greenwood R, Bennink JR, Yewdell JW, Frelinger JA. Multiple paths for activation of naive CD8+ T cells: CD4-independent help. J Immunol 2001;167:1283-9.
44. Gammon DB, Gowrishankar B, Duraffour S, Andrei G, Upton C, Evans DH. Vaccinia virus-encoded ribonucleotide reductase subunits are differentially required for replication and pathogenesis. PLoS Pathog 2010;6:e1000984.
45. Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 2011;477:99-102.
46. Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov 2015;14:642-62.
47. Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 2012;12:180-90.
48. Paulos CM, Wrzesinski C, Kaiser A, Hinrichs CS, Chieppa M, Cassard L, et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J Clin Invest 2007;117:2197-204.
49. Devaud C, John LB, Westwood JA, Darcy PK, Kershaw MH. Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy. Oncoimmunology 2013;2:e25961.
50. Gajewski TF. The next hurdle in cancer immunotherapy: overcoming the non-T-cell-inflamed tumor microenvironment. Semin Oncol 2015;42:663-71.
51. Devaud C, Westwood JA, John LB, Flynn JK, Paquet-Fifield S, Duong CP, et al. Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy. Mol Ther 2014;22:18-27.
52. Slaney CY, Kershaw MH, Darcy PK. Trafficking of T cells into tumors. Cancer Res 2014;74:7168-74.
53. Hickman HD, Reynoso GV, Ngudiankama BF, Cush SS, Gibbs J, Bennink JR, et al. CXCR3 chemokine receptor enables local CD8(+) T cell migration for the destruction of virus-infected cells. Immunity 2015;42:524-37.
54. Ribas A, Timmerman JM, Butterfield LH, Economou JS. Determinant spreading and tumor responses after peptide-based cancer immunotherapy. Trends Immunol 2003;24:58-61.
55. Beatty GL, Haas AR, Maus MV, Torigian DA, Soulen MC, Plesa G, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2014;2:112-20.
56. Bollard CM, Gottschalk S, Torrano V, Diouf O, Ku S, Hazrat Y, et al. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol 2014;32:798-808.
57. Cruz CR, Micklethwaite KP, Savoldo B, Ramos CA, Lam S, Ku S, 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;122:2965-73.
58. Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 2011;118:6050-6.
59. Pule MA, Savoldo B, Myers GD, Rossig C, Russell HV, Dotti G, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 2008;14:1264-70.
60. Lamers CH, Sleijfer S, Vulto AG, Kruit WH, Kliffen M, Debets R, 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:e20-2.
61. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010;18:843-51.
62. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013;368:1509-18.
63. Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med 2013;5:215ra172.
64. Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol 2012;31:71-5.