Feasibility and safety of RNA-transfected CD20-specific chimeric antigen receptor T cells in dogs with spontaneous B cell lymphoma

Molecular Therapy

Volumn 24, Issue 9, 2016, Pages 1602-1614

  Panjwani, M Kazim ^a   Smith, Jenessa B ^b   Schutsky, Keith ^b   Gnanandarajah, Josephine ^a   O'Connor, Colleen M ^c   Powell, Daniel J ^b   Mason, Nicola J ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c CAVU Biotherapies   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD20 ANTIGEN; CHIMERIC ANTIGEN RECEPTOR; GAMMA INTERFERON; MESSENGER RNA; RNA; ANTINEOPLASTIC AGENT; CYCLOPHOSPHAMIDE; DOXORUBICIN; INTERLEUKIN 2; INTERLEUKIN 21; INTERLEUKIN DERIVATIVE; LYMPHOCYTE ANTIGEN RECEPTOR; PREDNISONE; VINCRISTINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN PRESENTING CELL; ANTIGEN SPECIFICITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; B CELL LYMPHOMA; CANCER REGRESSION; CELL THERAPY; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOLYSIS; DOG; DRUG SAFETY; DRUG TOLERABILITY; ELECTROPORATION; FEASIBILITY STUDY; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; LYMPHOMA; NONHUMAN; PROTEIN EXPRESSION; T LYMPHOCYTE; ADOPTIVE IMMUNOTHERAPY; ANIMAL; DRUG EFFECTS; GENE EXPRESSION; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; LYMPHOMA, B-CELL; METABOLISM; MOUSE; PROCEDURES; TREATMENT OUTCOME; TUMOR CELL LINE;

ANIMALS; ANTIGEN-PRESENTING CELLS; ANTIGENS, CD20; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL LINE, TUMOR; CYCLOPHOSPHAMIDE; DOGS; DOXORUBICIN; ELECTROPORATION; GENE EXPRESSION; HUMANS; IMMUNOTHERAPY, ADOPTIVE; INTERLEUKIN-2; INTERLEUKINS; LYMPHOCYTE ACTIVATION; LYMPHOMA, B-CELL; MICE; PREDNISONE; RECEPTORS, ANTIGEN, T-CELL; RNA, MESSENGER; T-LYMPHOCYTES; TRANSFECTION; TREATMENT OUTCOME; VINCRISTINE;

EID: 84983041155     PISSN: 15250016     EISSN: 15250024     Source Type: Journal    
DOI: 10.1038/mt.2016.146     Document Type: Article

References (63)

1. Gross, G, Waks, T, and Eshhar, Z. (1989). Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci USA 86: 10024-10028
2. Porter, DL, Hwang, WT, Frey, NV, Lacey, SF, Shaw, PA, Loren, AW, et al. (2015). Chimeric antigen receptor T cells persist, and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 7: 303ra139
3. Porter, DL, Levine, BL, Kalos, M, Bagg, A, and June, CH. (2011). Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365: 725-733
4. Grupp, SA, Kalos, M, Barrett, D, Aplenc, R, Porter, DL, Rheingold, SR, et al. (2013). Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368: 1509-1518
5. Maude, SL, Frey, N, Shaw, PA, Aplenc, R, Barrett, DM, Bunin, NJ, et al. (2014). Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371: 1507-1517
6. Chen, BJ, Chapuy, B, Ouyang, J, Sun, HH, Roemer, MG, Xu, ML, et al. (2013). PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas, and virusassociated malignancies. Clin Cancer Res 19: 3462-3473
7. Textor, A, Listopad, JJ, Wührmann, LL, Perez, C, Kruschinski, A, Chmielewski, M, et al. (2014). Efficacy of CAR T-cell therapy in large tumors relies upon stromal targeting by IFN. Cancer Res 74: 6796-6805
8. Beatty, GL, Haas, AR, Maus, MV, Torigian, DA, Soulen, MC, Plesa, G, et al. (2014). Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce antitumor activity in solid malignancies. Cancer Immunol Res 2: 112-120
9. Moon, EK, Wang, LC, Dolfi, DV, Wilson, CB, Ranganathan, R, Sun, J, et al. (2014). Multifactorial T-cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor-transduced human T cells in solid tumors. Clin Cancer Res 20: 4262-4273
10. Caruana, I, Savoldo, B, Hoyos, V, Weber, G, Liu, H, Kim, ES, et al. (2015). Heparanase promotes tumor infiltration, and antitumor activity of CAR-redirected T lymphocytes. Nat Med 21: 524-529
11. Lo, A, Wang, LC, Scholler, J, Monslow, J, Avery, D, Newick, K, et al. (2015). Tumorpromoting desmoplasia is disrupted by depleting FAP-expressing stromal cells. Cancer Res 75: 2800-2810
12. Di Stasi, A, De Angelis, B, Rooney, CM, Zhang, L, Mahendravada, A, Foster, AE, et al. (2009). T lymphocytes coexpressing CCR4, and a chimeric antigen receptor targeting CD30 have improved homing, and antitumor activity in a Hodgkin tumor model. Blood 113: 6392-6402
13. Hoyos, V, Savoldo, B, Quintarelli, C, Mahendravada, A, Zhang, M, Vera, J, et al. (2010). Engineering CD19-specific T lymphocytes with interleukin-15, and a suicide gene to enhance their anti-lymphoma/leukemia effects, and safety. Leukemia 24: 1160-1170
14. Urbanska, K, Lanitis, E, Poussin, M, Lynn, RC, Gavin, BP, Kelderman, S, et al. (2012). A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res 72: 1844-1852
15. Lanitis, E, Poussin, M, Klattenhoff, AW, Song, D, Sandaltzopoulos, R, June, CH, et al. (2013). Chimeric antigen receptor T Cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo. Cancer Immunol Res 1: 43-53
16. Fedorov, VD, Themeli, M, and Sadelain, M. (2013). PD-1-and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med 5: 215ra172
17. Ankri, C, Shamalov, K, Horovitz-Fried, M, Mauer, S, and Cohen, CJ. (2013). Human T cells engineered to express a programmed death 1/28 costimulatory retargeting molecule display enhanced antitumor activity. J Immunol 191: 4121-4129
18. Straathof, KC, Pulè, MA, Yotnda, P, Dotti, G, Vanin, EF, Brenner, MK, et al. (2005). An inducible caspase 9 safety switch for T-cell therapy. Blood 105: 4247-4254
19. Torikai, H, Reik, A, Liu, PQ, Zhou, Y, Zhang, L, Maiti, S, et al. (2012). A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor, and eliminate expression of endogenous TCR. Blood 119: 5697-5705
20. Kalos, M, Levine, BL, Porter, DL, Katz, S, Grupp, SA, Bagg, A, et al. (2011). T cells with chimeric antigen receptors have potent antitumor effects, and can establish memory in patients with advanced leukemia. Sci Transl Med 3: 95ra73
21. Morgan, RA, Yang, JC, Kitano, M, Dudley, ME, Laurencot, CM, and Rosenberg, SA. (2010). 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
22. Linette, GP, Stadtmauer, EA, Maus, MV, Rapoport, AP, Levine, BL, Emery, L, et al. (2013). Cardiovascular toxicity, and titin cross-reactivity of affinity-enhanced T cells in myeloma, and melanoma. Blood 122: 863-871
23. Lamers, CH, Sleijfer, S, van Steenbergen, S, van Elzakker, P, van Krimpen, B, Groot, C, et al. (2013). Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation, and management of on-target toxicity. Mol Ther 21: 904-912
24. Morgan, RA, Chinnasamy, N, Abate-Daga, D, Gros, A, Robbins, PF, Zheng, Z, et al. (2013). Cancer regression, and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36: 133-151
25. Steplewski, Z, Jeglum, KA, Rosales, C, and Weintraub, N. (1987). Canine lymphomaassociated antigens defined by murine monoclonal antibodies. Cancer Immunol Immunother 24: 197-201
26. Modiano, JF, Breen, M, Valli, VE, Wojcieszyn, JW, and Cutter, GR. (2007). Predictive value of p16 or Rb inactivation in a model of naturally occurring canine non-Hodgkin's lymphoma. Leukemia 21: 184-187
27. Breen, M, and Modiano, JF. (2008). Evolutionarily conserved cytogenetic changes in hematological malignancies of dogs, and humans-man, and his best friend share more than companionship. Chromosome Res 16: 145-154
28. Jubala, CM, Wojcieszyn, JW, Valli, VE, Getzy, DM, Fosmire, SP, Coffey, D, et al. (2005). CD20 expression in normal canine B cells, and in canine non-Hodgkin lymphoma. Vet Pathol 42: 468-476
29. O'Connor, CM, Sheppard, S, Hartline, CA, Huls, H, Johnson, M, Palla, SL, et al. (2012). Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy. Sci Rep 2: 249
30. Marconato, L, Gelain, ME, and Comazzi, S. (2013). The dog as a possible animal model for human non-Hodgkin lymphoma: a review. Hematol Oncol 31: 1-9
31. Mata, M, Vera, JF, Gerken, C, Rooney, CM, Miller, T, Pfent, C, et al. (2014). Toward immunotherapy with redirected T cells in a large animal model: ex vivo activation, expansion, and genetic modification of canine T cells. J Immunother 37: 407-415
32. Ito, D, Frantz, AM, and Modiano, JF. (2014). Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress, and applications. Vet Immunol Immunopathol 159: 192-201
33. Schiffman, JD, and Breen, M. (2015). Comparative oncology: what dogs, and other species can teach us about humans with cancer. Philos Trans R Soc Lond B Biol Sci 370
34. Kalos, M, and June, CH. (2013). Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity 39: 49-60
35. Baron, F, Sandmaier, BM, Zellmer, E, Sorror, M, Storer, B, and Storb, R. (2006). Failure of donor lymphocyte infusion to prevent graft rejection in dogs given DLA-identical marrow after 1 Gy of total body irradiation. Biol Blood Marrow Transplant 12: 813-817
36. Jochum, C, Beste, M, Zellmer, E, Graves, SS, and Storb, R. (2007). CD154 blockade, and donor-specific transfusions in DLA-identical marrow transplantation in dogs conditioned with 1-Gy total body irradiation. Biol Blood Marrow Transplant 13: 164-171
37. Chen, Y, Fukuda, T, Thakar, MS, Kornblit, BT, Storer, BE, Santos, EB, et al. (2011). Immunomodulatory effects induced by cytotoxic T lymphocyte antigen 4 immunoglobulin with donor peripheral blood mononuclear cell infusion in canine major histocompatibility complex-haplo-identical non-myeloablative hematopoietic cell transplantation. Cytotherapy 13: 1269-1280
38. Sato, M, Storb, R, Loretz, C, Stone, D, Mielcarek, M, Sale, GE, et al. (2013). Inducible costimulator (ICOS) up-regulation on activated T cells in chronic graft-versus-host disease after dog leukocyte antigen-nonidentical hematopoietic cell transplantation: a potential therapeutic target. Transplantation 96: 34-41
39. Maekawa, N, Konnai, S, Ikebuchi, R, Okagawa, T, Adachi, M, Takagi, S, et al. (2014). Expression of PD-L1 on canine tumor cells, and enhancement of IFN-?production from tumor-infiltrating cells by PD-L1 blockade. PLoS One 9: e98415
40. Kato, M, Watarai, S, Nishikawa, S, Iwasaki, T, and Kodama, H. (2007). A novel culture method of canine peripheral blood lymphocytes with concanavalin a, and recombinant human interleukin-2 for adoptive immunotherapy. J Vet Med Sci 69: 481-486
41. Graves, SS, Stone, DM, Loretz, C, Peterson, LJ, Lesnikova, M, Hwang, B, et al. (2011). Antagonistic, and agonistic anti-canine CD28 monoclonal antibodies: tools for allogeneic transplantation. Transplantation 91: 833-840
42. Levine, BL, Bernstein, WB, Connors, M, Craighead, N, Lindsten, T, Thompson, CB, et al. (1997). Effects of CD28 costimulation on long-term proliferation of CD4+ T cells in the absence of exogenous feeder cells. J Immunol 159: 5921-5930
43. Maus, MV, Thomas, AK, Leonard, DG, Allman, D, Addya, K, Schlienger, K, et al. (2002). 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 20: 143-148
44. Suhoski, MM, Golovina, TN, Aqui, NA, Tai, VC, Varela-Rohena, A, Milone, MC, et al. (2007). Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules. Mol Ther 15: 981-988
45. Bucher, C, Koch, L, Vogtenhuber, C, Goren, E, Munger, M, Panoskaltsis-Mortari, A, et al. (2009). IL-21 blockade reduces graft-versus-host disease mortality by supporting inducible T regulatory cell generation. Blood 114: 5375-5384
46. Bismarck, D, Schütze, N, Moore, P, Büttner, M, Alber, G, and Buttlar, Hv. (2012). Canine CD4+CD8+ double positive T cells in peripheral blood have features of activated T cells. Vet Immunol Immunopathol 149: 157-166
47. Nadler, LM, Ritz, J, Hardy, R, Pesando, JM, Schlossman, SF, and Stashenko, P. (1981). A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest 67: 134-140
48. Ito, D, Brewer, S, Modiano, JF, and Beall, MJ. (2015). Development of a novel anticanine CD20 monoclonal antibody with diagnostic, and therapeutic potential. Leuk Lymphoma 56: 219-225
49. Maus, MV, Haas, AR, Beatty, GL, Albelda, SM, Levine, BL, Liu, X, et al. (2013). T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res 1: 26-31
50. Kershaw, MH, Westwood, JA, Parker, LL, Wang, G, Eshhar, Z, Mavroukakis, SA, et al. (2006). A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 12(20 Pt 1): 6106-6115
51. National Cancer Policy Forum, Board on Health Care Services, Institute of Medicine, National Academies of Sciences, Engineering, and Medicine. (2015). The Role of Clinical Studies for Pets with Naturally Occurring Tumors in Translational Cancer Research: Workshop Summary. National Academies Press: Washington, DC
52. Schutsky, K, Song, DG, Lynn, R, Smith, JB, Poussin, M, Figini, M, et al. (2015). Rigorous optimization, and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor. Oncotarget 6: 28911-28928
53. Zhao, Y, Moon, E, Carpenito, C, Paulos, CM, Liu, X, Brennan, AL, et al. (2010). Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res 70: 9053-9061
54. Geiger, TL, Nguyen, P, Leitenberg, D, and Flavell, RA. (2001). Integrated src kinase, and costimulatory activity enhances signal transduction through single-chain chimeric receptors in T lymphocytes. Blood 98: 2364-2371
55. Finney, HM, Akbar, AN, and Lawson, AD. (2004). Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol 172: 104-113
56. Milone, MC, Fish, JD, Carpenito, C, Carroll, RG, Binder, GK, Teachey, D, et al. (2009). Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells, and increased antileukemic efficacy in vivo. Mol Ther 17: 1453-1464
57. Carpenito, C, Milone, MC, Hassan, R, Simonet, JC, Lakhal, M, Suhoski, MM, et al. (2009). Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28, and CD137 domains. Proc Natl Acad Sci USA 106: 3360-3365
58. Song, DG, Ye, Q, Carpenito, C, Poussin, M, Wang, LP, Ji, C, et al. (2011). In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB). Cancer Res 71: 4617-4627
59. Long, AH, Haso, WM, Shern, JF, Wanhainen, KM, Murgai, M, Ingaramo, M, et al. (2015). 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med 21: 581-590
60. Reiser, J. (2000). Production, and concentration of pseudotyped HIV-1-based gene transfer vectors. Gene Ther 7: 910-913
61. Parry, RV, Rumbley, CA, Vandenberghe, LH, June, CH, and Riley, JL. (2003). CD28, and inducible costimulatory protein Src homology 2 binding domains show distinct regulation of phosphatidylinositol 3-kinase, Bcl-xL, and IL-2 expression in primary human CD4 T lymphocytes. J Immunol 171: 166-174
62. O'Connor, CM, Olivares, S, Ang, S, Champlin, RE, Wilson-Robles, HM, and Cooper, LJ. (2013). Chimeric antigen receptor T-cell therapy for companion canines with spontaneous B-cell non-Hodgkin lymphoma. Mol Ther 21: S249
63. Gaurnier-Hausser, A, Patel, R, Baldwin, AS, May, MJ, and Mason, NJ. (2011). NEMObinding domain peptide inhibits constitutive NF-B activity, and reduces tumor burden in a canine model of relapsed, refractory diffuse large B-cell lymphoma. Clin Cancer Res 17: 4661-4671