Overcoming the toxicity hurdles of genetically targeted T cells

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• 作者：Monica Casucci (1)
  Robert E. Hawkins (2)
  Gianpietro Dotti (3)
  Attilio Bondanza (4)
  
  1. Innovative Immunotherapies Unit ; Division of Immunology ; Transplantation and Infectious Diseases ; San Raffaele Hospital Scientific Institute ; Via Olgettina 60 ; 20132 ; Milan ; Italy
  2. Cancer Research UK ; Department of Medical Oncology ; University of Manchester and Christie Hospital NHS Foundation Trust ; Wilmslow Road ; Withington ; Manchester ; M20 4BX ; UK
  3. Center for Cell and Gene Therapy ; Baylor College of Medicine ; 6621 Fannin St. MC 3-3320 ; Houston ; TX ; 77030 ; USA
  4. Innovative Immunotherapies Unit ; Division of Immunology ; Transplantation and Infectious Diseases ; San Raffaele Hospital Scientific Institute ; Vita-Salute San Raffaele University ; Via Olgettina 60 ; 20132 ; Milan ; Italy
  
• 关键词：Adoptive immunotherapy ; Genetically modified T cells ; Suicide genes ; NIBIT 2013
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：64
• 期：1
• 页码：123-130
• 全文大小：316 KB
• 参考文献：1. Dotti G, Gottschalk S, Savoldo B, Brenner MK (2014) Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev 257:107鈥?26. doi:10.1111/imr.12131 2131" target="_blank" title="It opens in new window">CrossRef
  2. Jensen MC, Riddell SR (2014) Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunol Rev 257:127鈥?44. doi:10.1111/imr.12139 2139" target="_blank" title="It opens in new window">CrossRef
  3. Maus MV, Grupp SA, Porter DL, June CH (2014) Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123:2625鈥?635. doi:10.1182/blood-2013-11-492231 2/blood-2013-11-492231" target="_blank" title="It opens in new window">CrossRef
  4. Porter DL, Levine BL, Kalos M, Bagg A, June CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365:725鈥?33. doi:10.1056/NEJMoa1103849 CrossRef
  5. Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH (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. doi:10.1126/scitranslmed.3002842
  6. Brentjens RJ, Davila ML, Riviere I et al (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 5:177ra138. doi: 10.1126/scitranslmed.3005930
  7. Grupp SA, Kalos M, Barrett D et al (2013) Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368:1509鈥?518. doi:10.1056/NEJMoa1215134 215134" target="_blank" title="It opens in new window">CrossRef
  8. Robbins PF, Morgan RA, Feldman SA et al (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 29:917鈥?24. doi:10.1200/JCO.2010.32.2537 200/JCO.2010.32.2537" target="_blank" title="It opens in new window">CrossRef
  9. Morgan RA, Dudley ME, Wunderlich JR et al (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126鈥?29. doi:10.1126/science.1129003 26/science.1129003" target="_blank" title="It opens in new window">CrossRef
  10. Johnson LA, Morgan RA, Dudley ME et al (2009) Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:535鈥?46. doi:10.1182/blood-2009-03-211714 2/blood-2009-03-211714" target="_blank" title="It opens in new window">CrossRef
  11. Parkhurst MR, Yang JC, Langan RC et al (2011) T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 19:620鈥?26. doi:10.1038/mt.2010.272 2010.272" target="_blank" title="It opens in new window">CrossRef
  12. Cameron BJ, Gerry AB, Dukes J et al (2013) 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. doi:10.1126/scitranslmed.3006034
  13. Linette GP, Stadtmauer EA, Maus MV et al (2013) Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122:863鈥?71. doi:10.1182/blood-2013-03-490565 2/blood-2013-03-490565" target="_blank" title="It opens in new window">CrossRef
  14. Bendle GM, Linnemann C, Hooijkaas AI et al (2010) Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med 16:565鈥?70. doi:10.1038/nm.2128 2128" target="_blank" title="It opens in new window">CrossRef
  15. Scholten KB, Kramer D, Kueter EW, Graf M, Schoedl T, Meijer CJ, Schreurs MW, Hooijberg E (2006) Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells. Clin Immunol 119:135鈥?45. doi:10.1016/j.clim.2005.12.009 2005.12.009" target="_blank" title="It opens in new window">CrossRef
  16. Cohen CJ, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA (2006) Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res 66:8878鈥?886. doi:10.1158/0008-5472.CAN-06-1450 2.CAN-06-1450" target="_blank" title="It opens in new window">CrossRef
  17. Kuball J, Dossett ML, Wolfl M, Ho WY, Voss RH, Fowler C, Greenberg PD (2007) Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 109:2331鈥?338. doi:10.1182/blood-2006-05-023069 2/blood-2006-05-023069" target="_blank" title="It opens in new window">CrossRef
  18. Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, Kato I (2009) Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res 69:9003鈥?011. doi:10.1158/0008-5472.CAN-09-1450 2.CAN-09-1450" target="_blank" title="It opens in new window">CrossRef
  19. Provasi E, Genovese P, Lombardo A et al (2012) Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med 18:807鈥?15. doi:10.1038/nm.2700 2700" target="_blank" title="It opens in new window">CrossRef
  20. Hombach A, Hombach AA, Abken H (2010) Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc 鈥榮pacer鈥?domain in the extracellular moiety of chimeric antigen receptors avoids 鈥榦ff-target鈥?activation and unintended initiation of an innate immune response. Gene Ther 17:1206鈥?213. doi:10.1038/gt.2010.91 2010.91" target="_blank" title="It opens in new window">CrossRef
  21. Lamers CH, Sleijfer S, Vulto AG, Kruit WH, Kliffen M, Debets R, Gratama JW, Stoter G, Oosterwijk E (2006) Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol 24:e20鈥揺22. doi:10.1200/JCO.2006.05.9964 200/JCO.2006.05.9964" target="_blank" title="It opens in new window">CrossRef
  22. Savoldo B, Ramos CA, Liu E et al (2011) CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 121:1822鈥?826. doi:10.1172/JCI46110 2/JCI46110" target="_blank" title="It opens in new window">CrossRef
  23. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, 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鈥?51. doi:10.1038/mt.2010.24 2010.24" target="_blank" title="It opens in new window">CrossRef
  24. Morgan RA, Chinnasamy N, Abate-Daga D et al (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36:133鈥?51. doi:10.1097/CJI.0b013e3182829903 2829903" target="_blank" title="It opens in new window">CrossRef
  25. Tettamanti S, Marin V, Pizzitola I et al (2013) Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor. Br J Haematol 161:389鈥?01. doi:10.1111/bjh.12282 2282" target="_blank" title="It opens in new window">CrossRef
  26. Gill S, Tasian SK, Ruella M et al (2014) Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood 123:2343鈥?354. doi:10.1182/blood-2013-09-529537 2/blood-2013-09-529537" target="_blank" title="It opens in new window">CrossRef
  27. Casucci M, Nicolis di Robilant B, Falcone L et al (2013) CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 122:3461鈥?672. doi:10.1182/blood-2013-04-493361 2/blood-2013-04-493361" target="_blank" title="It opens in new window">CrossRef
  28. Brentjens RJ, Riviere I, Park JH et al (2011) Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 118:4817鈥?828. doi:10.1182/blood-2011-04-348540 2/blood-2011-04-348540" target="_blank" title="It opens in new window">CrossRef
  29. Teachey DT, Rheingold SR, Maude SL et al (2013) Cytokine-release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 121:5154鈥?157. doi:10.1182/blood-2013-02-485623 2/blood-2013-02-485623" target="_blank" title="It opens in new window">CrossRef
  30. Barrett DM, Teachey DT, Grupp SA (2014) Toxicity management for patients receiving novel T-cell engaging therapies. Curr Opin Pediatr 26:43鈥?9. doi:10.1097/MOP.0000000000000043 CrossRef
  31. Ertl HC, Zaia J, Rosenberg SA, June CH, Dotti G, Kahn J, Cooper LJ, Corrigan-Curay J, Strome SE (2011) 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 71:3175鈥?181. doi:10.1158/0008-5472.CAN-10-4035 2.CAN-10-4035" target="_blank" title="It opens in new window">CrossRef
  32. Davila ML, Riviere I, Wang X et al (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6:224ra225. doi:10.1126/scitranslmed.3008226
  33. Berger C, Flowers ME, Warren EH, Riddell SR (2006) 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 107:2294鈥?302. doi:10.1182/blood-2005-08-3503 2/blood-2005-08-3503" target="_blank" title="It opens in new window">CrossRef
  34. Traversari C, Marktel S, Magnani Z, Mangia P, Russo V, Ciceri F, Bonini C, Bordignon C (2007) The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies. Blood 109:4708鈥?715. doi:10.1182/blood-2006-04-015230 2/blood-2006-04-015230" target="_blank" title="It opens in new window">CrossRef
  35. Jensen MC, Popplewell L, Cooper LJ, DiGiusto D, Kalos M, Ostberg JR, Forman SJ (2010) Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol Blood Marrow Transpl 16:1245鈥?256. doi:10.1016/j.bbmt.2010.03.014 2010.03.014" target="_blank" title="It opens in new window">CrossRef
  36. Russo V, Bondanza A, Ciceri F, Bregni M, Bordignon C, Traversari C, Bonini C (2012) A dual role for genetically modified lymphocytes in cancer immunotherapy. Trends Mol Med 18:193鈥?00. doi:10.1016/j.molmed.2011.12.003 2011.12.003" target="_blank" title="It opens in new window">CrossRef
  37. Bonini C, Ferrari G, Verzeletti S et al (1997) HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276:1719鈥?724 26/science.276.5319.1719" target="_blank" title="It opens in new window">CrossRef
  38. Ciceri F, Bonini C, Stanghellini MT et al (2009) 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 10:489鈥?00. doi:10.1016/S1470-2045(09)70074-9 2045(09)70074-9" target="_blank" title="It opens in new window">CrossRef
  39. Oliveira G, Greco R, Lupo-Stanghellini MT, Vago L (2012) Bonini C Use of TK-cells in haploidentical hematopoietic stem cell transplantation. Curr Opin Hematol 19:427鈥?33. doi:10.1097/MOH.0b013e32835822f5 2835822f5" target="_blank" title="It opens in new window">CrossRef
  40. Garin MI, Garrett E, Tiberghien P, Apperley JF, Chalmers D, Melo JV, Ferrand C (2001) Molecular mechanism for ganciclovir resistance in human T lymphocytes transduced with retroviral vectors carrying the herpes simplex virus thymidine kinase gene. Blood 97:122鈥?29 2/blood.V97.1.122" target="_blank" title="It opens in new window">CrossRef
  41. Chalmers D, Ferrand C, Apperley JF et al (2001) Elimination of the truncated message from the herpes simplex virus thymidine kinase suicide gene. Mol Ther 4:146鈥?48. doi:10.1006/mthe.2001.0433 2001.0433" target="_blank" title="It opens in new window">CrossRef
  42. Straathof KC, Pule MA, Yotnda P, Dotti G, Vanin EF, Brenner MK, Heslop HE, Spencer DM, Rooney CM (2005) An inducible caspase 9 safety switch for T-cell therapy. Blood 105:4247鈥?254. doi:10.1182/blood-2004-11-4564 2/blood-2004-11-4564" target="_blank" title="It opens in new window">CrossRef
  43. Di Stasi A, Tey SK, Dotti G et al (2011) Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 365:1673鈥?683. doi:10.1056/NEJMoa1106152 2" target="_blank" title="It opens in new window">CrossRef
  44. Zhou X, Di Stasi A, Tey SK et al (2014) Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood 123:3895鈥?905. doi:10.1182/blood-2014-01-551671 2/blood-2014-01-551671" target="_blank" title="It opens in new window">CrossRef
  45. Hoyos V, Savoldo B, Quintarelli C 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鈥?170. doi:10.1038/leu.2010.75 2010.75" target="_blank" title="It opens in new window">CrossRef
  46. Beatty GL, Haas AR, Maus MV et al (2014) Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2:112鈥?20. doi:10.1158/2326-6066.CIR-13-0170 2326-6066.CIR-13-0170" target="_blank" title="It opens in new window">CrossRef
  47. Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M (2013) Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol 31:71鈥?5. doi:10.1038/nbt.2459 2459" target="_blank" title="It opens in new window">CrossRef
  48. Fedorov VD, Themeli M, Sadelain M (2013) PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med 5:215ra172. doi:10.1126/scitranslmed.3006597
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

The recent successes of clinical trials with T cells genetically modified with either clonal T cell receptors or chimeric antigen receptors have also highlighted their potential toxicities. The aim of this focused review was to describe the adverse events observed in these clinical trials and to link them to the complex biology of genetically targeted T cells. Finally, strategies to overcome these toxicities will be proposed and discussed, including the use of suicide genes and other innovative gene therapy strategies.