Adoptive T-cell therapy: adverse events and safety switches

Clinical and Translational Immunology

Volumn 3, Issue 6, 2014, Pages

  Tey, Siok Keen ^a,b,c  

^a QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^b ROYAL BRISBANE AND WOMEN'S HOSPITAL   (Australia)

^c UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84931033757     PISSN: None     EISSN: 20500068     Source Type: Journal    
DOI: 10.1038/cti.2014.11     Document Type: Review

References (64)

1. Drobyski WR, Keever CA, Roth MS, Koethe S, Hanson G, McFadden P et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood 1993; 82: 2310–2318.
2. Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990; 76: 2462–2465.
3. Collins RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.
4. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 1992; 257: 238–241.
5. Rooney CM, Smith CA, Ng CY, Loftin S, Li C, Krance RA et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 1995; 345: 9–13.
6. Heslop HE, Ng CY, Li C, Smith CA, Loftin SK, Krance RA et al. Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med 1996; 2: 551–555.
7. Khanna R, Bell S, Sherritt M, Galbraith A, Burrows SR, Rafter L et al. Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease. Proc Natl Acad Sci USA 1999; 96: 10391–10396.
8. Comoli P, Labirio M, Basso S, Baldanti F, Grossi P, Furione M et al. Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood 2002; 99: 2592–2598.
9. Yee C, Savage PA, Lee PP, Davis MM, Greenberg PD. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers. J Immunol 1999; 162: 2227–2234.
10. Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS et al. Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 1994; 86: 1159–1166.
11. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126–129.
12. Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev 2014; 257: 107–126.
13. Jena B, Dotti G, Cooper LJ. Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood 2010; 116: 1035–1044.
14. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. New Engl J Med 2013; 368: 1509–1518.
15. Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 2012; 119: 2709–2720.
16. Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 2013; 10: 267–276.
17. Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013; 5: 177ra38.
18. 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.
19. Cruz CR, Hanley PJ, Liu H, Torrano V, Lin YF, Arce JA et al. Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience. Cytotherapy 2010; 12: 743–749.
20. Mitsuyasu RT, Champlin RE, Gale RP, Ho WG, Lenarsky C, Winston D et al. Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. A prospective, randomized, double-blind trial. Ann Intern Med 1986; 105: 20–26.
21. Apperley JF, Jones L, Hale G, Waldmann H, Hows J, Rombos Y et al. Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. Bone Marrow Transplant 1986; 1: 53–66.
22. Maraninchi D, Gluckman E, Blaise D, Guyotat D, Rio B, Pico JL et al. Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias. Lancet 1987; 2: 175–178.
23. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298: 850–854.
24. Yee C, Thompson JA, Roche P, Byrd DR, Lee PP, Piepkorn M et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo. J Exp Med 2000; 192: 1637–1644.
25. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009; 114: 535–546.
26. 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: 843–851.
27. Lamers CH, Sleijfer S, van Steenbergen S, van Elzakker P, van Krimpen B, Groot C et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther 2013; 21: 904–912.
28. Lamers CHJ, Sleijfer S, Vulto AG, Kruit WHJ, 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–e22.
29. Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA, Feldman SA et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 2011; 19: 620–626.
30. 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: 133–151.
31. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. New Engl J Med 2011; 365: 725–733.
32. Grupp SA, Porter DL, Teachey DT, Barrett DM, Chew A, Suppa E et al. CD19-redirected chimeric antigen receptor T (CART19) cells induce a cytokine release syndrome (CRS) and induction of treatable macrophage activation syndrome (MAS) that can be managed by the IL-6 antagonist Tocilizumab (toc). ASH Annu Meet Abstr 2012; 120: 2604.
33. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 2013; 122: 863–871.
34. Cameron BJ, Gerry AB, Dukes J, Harper JV, Kannan V, Bianchi FC et al. Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci Transl Med 2013; 5: 197ra03.
35. 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 USA 2010; 107: 10972–10977.
36. Bendle GM, Linnemann C, Hooijkaas AI, Bies L, de Witte MA, Jorritsma A et al. Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med 2010; 16: 565–570.
37. Rosenberg SA. Of mice, not men: no evidence for graft-versus-host disease in humans receiving T-cell receptor-transduced autologous T cells. Mol Ther 2010; 18: 1744–1745.
38. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118: 3132–3142.
39. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest 2008; 118: 3143–3150.
40. Stein S, Ott MG, Schultze-Strasser S, Jauch A, Burwinkel B, Kinner A et al. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med 2010; 16: 198–204.
41. Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A, Rothe M et al. Gene therapy for Wiskott-Aldrich syndrome–long-term efficacy and genotoxicity. Sci Transl Med 2014; 6: 227ra33.
42. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997; 276: 1719–1724.
43. Tiberghien P, Ferrand C, Lioure B, Milpied N, Angonin R, Deconinck E et al. Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft. Blood 2001; 97: 63–72.
44. Tiberghien P, Reynolds C, Keller J, Spence S, Deschaseaux M, Certoux J et al. Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation? Blood 1994; 84: 1333–1341.
45. Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol 2009; 10: 489–500.
46. Berger C, Flowers ME, Warren EH, Riddell SR. Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood 2006; 107: 2294–2302.
47. Garin MI, Garrett E, Tiberghien P, Apperley JF, Chalmers D, Melo JV et al. Molecular mechanism for ganciclovir resistance in human T lymphocytes transduced with retroviral vectors carrying the herpes simplex virus thymidine kinase gene. Blood 2001; 97: 122–129.
48. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C et al. Inducible apoptosis as a safety switch for adoptive cell therapy. New Engl J Med 2011; 365: 1673–1683.
49. Spencer DM, Wandless TJ, Schreiber SL, Crabtree GR. Controlling signal transduction with synthetic ligands. Science 1993; 262: 1019–1024.
50. Clackson T, Yang W, Rozamus LW, Hatada M, Amara JF, Rollins CT et al. Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci USA 1998; 95: 10437–10442.
51. Belshaw PJ, Spencer DM, Crabtree GR, Schreiber SL. Controlling programmed cell death with a cyclophilin-cyclosporin-based chemical inducer of dimerization. Chem Biol 1996; 3: 731–738.
52. MacCorkle RA, Freeman KW, Spencer DM. Synthetic activation of caspases: artificial death switches. Proc Natl Acad Sci USA 1998; 95: 3655–3660.
53. Spencer DM, Belshaw PJ, Chen L, Ho SN, Randazzo F, Crabtree GR et al. Functional analysis of Fas signaling in vivo using synthetic inducers of dimerization. Curr Biol 1996; 6: 839–847.
54. Straathof KC, Pule MA, Yotnda P, Dotti G, Vanin EF, Brenner MK et al. An inducible caspase 9 safety switch for T-cell therapy. Blood 2005; 105: 4247–4254.
55. Tey SK, Dotti G, Rooney CM, Heslop HE, Brenner MK. Inducible caspase 9 suicide gene to improve the safety of allodepleted T cells after haploidentical stem cell transplantation. Biol Blood Marrow Transplant 2007; 13: 913–924.
56. Donnelly MLL, Luke G, Mehrotra A, Li X, Hughes LE, Gani D et al. Analysis of the aphthovirus 2A/2B polyprotein ‘cleavage’ mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal ‘skip’. J Gen Virol 2001; 82: 1013–1025.
57. Burns WR, Zheng Z, Rosenberg SA, Morgan RA. Lack of specific γ-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation. Blood 2009; 114: 2888–2899.
58. Arber C, Abhyankar H, Heslop HE, Brenner MK, Liu H, Dotti G et al. The immunogenicity of virus-derived 2A sequences in immunocompetent individuals. Gene Ther 2013; 20: 958–962.
59. Themeli M, Kloss CC, Ciriello G, Fedorov VD, Perna F, Gonen M et al. Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nat Biotechnol 2013; 31: 928–933.
60. Hippen KL, Merkel SC, Schirm DK, Nelson C, Tennis NC, Riley JL et al. Generation and large-scale expansion of human inducible regulatory T cells that suppress graft-versus-host disease. Am J Transplant 2011; 11: 1148–1157.
61. Hippen KL, Merkel SC, Schirm DK, Sieben CM, Sumstad D, Kadidlo DM et al. Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity. Sci Transl Med 2011; 3: 83ra41.
62. Zhang P, Tey SK, Koyama M, Kuns RD, Olver SD, Lineburg KE et al. Induced regulatory T cells promote tolerance when stabilized by rapamycin and IL-2 in vivo. J Immunol 2013; 191: 5291–5303.
63. Tey SK, Brenner MK. The continuing contribution of gene marking to cell and gene therapy. Mol Ther 2007; 15: 666–676.
64. Ertl HCJ, Zaia J, Rosenberg SA, June CH, Dotti G, Kahn J et al. Considerations for the clinical application of chimeric antigen receptor T cells: observations from a recombinant DNA Advisory Committee Symposium held June 15, 2010. Cancer Res 2011; 71: 3175–3181.