Адоптивная иммунотерапия генетически модифицированными Т-лимфоцитами, экспрессирующими химерные антигенные рецепторы
Аннотация
Значительная смертность от онкологических заболеваний в целом и онкогематологических в частности побуждает научно-медицинское сообщество к разработке новых методов лечения. Одним из новейших методов является адоптивная клеточная терапия с использованием генетически-модифицированных Т-лимфоцитов больного, экспрессирующих химерные антигенные рецепторы (CAR) к специфическим опухолевым антигенам. Несмотря на высокую стоимость и наличие осложнений в применении, многообещающие клинические испытания у больных даже на поздних стадиях онкозаболеваний позволяют раcсчитывать на успешное внедрение этого метода в практику.
В статье представлен обзор основных принципов данной технологии, опубликованных результатов клинических испытаний СAR T-клеток с акцентом на таргетирование антигена CD19, осложнений данной терапии, механизмов резистентности опухолей к действию CAR T-клеток и потенциальных путей ее преодоления.
Об авторах
А. А. Павлова
Сколковский институт науки и технологий, инновационный центр «Сколково»;
Мемориальный онкологический центр Слоун Кеттеринг;
Россия
Россия, 143026 Москва, ул. Нобеля, 3;
США, 10065 Нью-Йорк, Йорк-авеню 1275;
Россия
Россия, 143026 Москва, ул. Нобеля, 3;
США, 10065 Нью-Йорк, Йорк-авеню 1275;
М. А. Масчан
ФГБУ «Национальный научно-практический центр детской гематологии,
онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России;
Россия
Лаборатория клеточного гемостаза и тромбоза
Россия, 117997 Москва, ул. Саморы Машела, 1
Россия
Лаборатория клеточного гемостаза и тромбоза
Россия, 117997 Москва, ул. Саморы Машела, 1
В. Б. Пономарев
Мемориальный онкологический центр Слоун Кеттеринг;
Соединённые Штаты Америки
10065 Нью-Йорк, Йорк-авеню 1275;
Соединённые Штаты Америки
10065 Нью-Йорк, Йорк-авеню 1275;
Список литературы
1. Злокачественные новообразования в России в 2015 году (заболеваемость и смертность). Доступно по: http://www.oncology.ru/service/statistics/malignant_tumors. [Malignancies in Russia in 2015 (morbidity and mortality). Available at: http://www.oncology.ru/service/statistics/malignant_tumors. (In Russ.)].
2. Irving B.A., Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor – associated signal transduction pathways. Cell 1991;64:891–901. PMID: 1705867.
3. Romeo C., Amiot M., Seed B. Sequence requirements for induction of cytolysis by the T cell antigen/Fc receptor zets chain. Cell 1992;68:889–97. PMID: 1547489.
4. Eshhar Z., Waks T., Gross G., Schindler D.G. Specific activation and targeting of cytotoxic lymphocytes throught chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA 1993; 90:720–4. PMCID: PMC45737.
5. Newick K., Moon E., Albelda S.M. Chimeric antigen receptor T-cell therapy for solid tumors. Mol Ther Oncolytics 2016;3:16006. DOI: 10.1038/mto.2016.6.
6. Eshhar Z., Bach N., Fitzer-Attas C.J. et al. The T-body approach: potential for cancer immunotherapy. Springer Semin Immunopathol 1996;18(2):199–209. PMID: 8908700.
7. Gong M.C., Latouche J.B., Krause A. et al. Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen. Neoplasia 1999;1:123–7. PMID: 10933046.
8. Kershaw M.H., Westwood J.A., Parker L.L. et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 2006;12(20 pt 1):6106–15. DOI: 10.1158/1078-0432.CCR-06-1183.
9. Lamers C.H., Sleijfer S., Vulto A.G. 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;1;24(13):e20–2. DOI: 10.1200/JCO.2006.05.9964.
10. Haynes N.M., Trapani J.A., Teng M.W. et al. Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors. Blood 2002;100:3155–63. DOI: 10.1182/blood-2002-04-1041.
11. Hombach A., Heuser C., Marquardt T. et al. CD4+ T cells engrafted with a recombinant immunoreceptor ef ciently lyse target cells in a MHC antigen- and Fas-independent fashion. J Immunol 2001;167:1090–6. PMID: 11441120.
12. Kochenderfer J.N., Wilson W.H., Janik J.E. et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010;116(20): 4099–102. DOI: 10.1182/blood-2010-04-281931.
13. Gill S., Maus M.V., Porter D.L. Chimeric antigen receptor T cell therapy: 25 years in the making. Blood Rev 2016;30(3):157–67. DOI: 10.1016/j.blre.2015.10.003.
14. Wilkie S., Picco G., Foster J. et al. Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. J Immunol 2008;180:4901–9. PMID: 18354214.
15. Pule M.A., Straathof K.C., Dotti G. et al. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther 2005;12:933–41. DOI: 10.1016/j.ymthe.2005.04.016.
16. Wang J., Jensen M., Lin Y. et al. Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains. Hum Gene Ther 2007;18:712–25. DOI: 10.1089/hum.2007.028.
17. Maher J., Wilkie S. CAR mechanics: driving T cells into the MUC of cancer. Cancer Res 2009;69(11):4559–62. DOI: 10.1158/0008-5472.CAN-09-0564.
18. Sadelain M., Brentjens R., Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov 2013;3(4):388–98. DOI: 10.1158/2159-8290.CD-12-0548.
19. Gan H.K., Burgess A.W., Clayton A.H., Scott A.M. Targeting of a conformationally exposed, tumor-specific epitope of EGFR as a strategy for cancer therapy. Cancer Res 2012;72(12):2924–30. DOI: 10.1158/0008-5472.CAN-11-3898.
20. Sampson J.H., Heimberger A.B., Archer G.E. et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol 2010;28(31):4722–9. DOI: 10.1200/JCO.2010.28.6963.
21. Krogsgaard M., Davis M.M. How T cells ‘see’ antigen. Nat Immunol 2005;6:239–45. DOI: 10.1038/ni1173.
22. Rapoport A.P., Stadtmauer E.A., BinderScholl G.K. et al. NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med 2015;21(8):914–21. DOI: 10.1038/nm.3910.
23. Morgan R.A., Chinnasamy N., Abate-Daga D. et al. Cancer regression and neurologcal toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 2013;36(2):133–51. DOI: 10.1097/CJI.0b013e3182829903.
24. Kakarla S., Gottschalk S. CAR T cells for solid tumors: armed and ready to go? Cancer J 2014;20(2):151–5. DOI: 10.1097/PPO.0000000000000032.
25. Li Y.S., Wasserman R., Hayakawa K., Hardy R.R. Identification of the earliest B lineage stage in mouse bone marrow. Immunity 1996;5:527–35. PMID: 8986713.
26. Li Y.S., Hayakawa K., Hardy R.R. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J Exp Med 1993;178:951–60. PMCID: PMC2191150.
27. Maher J., Brentjens R.J., Gunset G. et al. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol 2002;20:70–5. DOI: 10.1038/nbt0102-70.
28. Davila M.L., Sadelain M. Biology and clinical application of CAR T cells for B cell malignancies. Int J Hematol 2016;104:6–17. DOI: 10.1007/s12185-016-2039-6.
29. Topp M.S., Gökbuget N., Stein A.S. et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2015 Jan;16(1):57–66. DOI: 10.1016/S1470-2045(14)71170-2.
30. Kochenderfer J.N., Rosenberg S.A. Treating B-cell cancer with T cells expressing antiCD19 chimeric antigen receptors. Nat Rev Clin Oncol 2013 May;10(5):267–76. DOI: 10.1038/nrclinonc.2013.46.
31. Wang X., Rivière I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics 2016;3:16015. DOI: 10.1038/mto.2016.15.
32. Kochenderfer J.N., Dudley M.E., Kassim S.H. 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. DOI: 10.1200/JCO.2014.56.2025.
33. Wang X., Stefanski J., Borquez-Ojeda O. et al. Comparison of CTS Dynabeadsc CD3/CD28, Miltenyi TransAct CD3/28 and ExpAct beads for large-scale CAR T cell manufacturing. European Society of Gene and Cell Therapy Collaborative Congress 2015, Helsinki, Finland. A31.
34. Vacchelli E., Vitale I., Eggermont A. et al. Trial watch: Dendritic cell-based interventions for cancer therapy. Oncoimmunology 2013;2:e25771. DOI: 10.4161/onci.25771.
35. Kim J.V., Latouche J.B., Rivière I., Sadelain M. The ABCs of artificial antigen presentation. Nat Biotechnol 2004;22:403–10. DOI: 10.1038/nbt955.
36. Bashour K.T., Graef P., Stemberger C. et al. Functional characterization of a T cell stimulation reagent for the production of therapeutic chimeric antigen receptor T cells. ASH 57th Annual Meeting & Exposition, 2015, Orlando, FL.
37. Sadelain M., Papapetrou E.P., Bushman F.D. Safe harbours for the integration of new DNA in the human genome. Nat Rev Cancer 2011;12(1):51–8. DOI: 10.1038/nrc3179.
38. Suerth J.D., Schambach A., Baum C. Genetic modification of lymphocytes by retrovirus-based vectors. Curr Opin Immunol 2012;24(5):598–608. DOI: 10.1016/j.coi.2012.08.007.
39. Ghani K., Wang X., de Campos-Lima P.O. et al. Efficient human hematopoietic cell transduction using RD114- and GALVpseudotyped retroviral vectors produced in suspension and serum-free media. Hum Gene Ther 2009;20:966–74. DOI: 10.1089/hum.2009.001.
40. Vannucci L., Lai M., Chiuppesi F. et al. Viral vectors: a look back and ahead on gene transfer technology. New Microbiol 2013;36:1–22. PMID: 23435812.
41. Throm R.E., Ouma A.A., Zhou S. et al. Efficient construction of producer cell lines for a SIN lentiviral vector for SCID-X1 gene therapy by concatemeric array transfection. Blood 2009;113:5104–10. DOI: 10.1182/blood-2008-11-191049.
42. Singh H., Huls H., Kebriaei P., Cooper L.J. A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19. Immunol Rev 2014;257:181–90. DOI: 10.1111/imr.12137.
43. Zhao Y., Zheng Z., Cohen C.J. et al. High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation. Mol Ther 2006;13(1):151–9. DOI: 10.1016/j.ymthe.2005.07.688.
44. Birkholz K., Hombach A., Krug C. et al. Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer. Gene Ther 2009;16(5):596–604. DOI: 10.1038/gt.2008.189.
45. Hollyman D., Stefanski J., Przybylowski M. et al. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. J Immunother 2009;32:169–80. DOI: 10.1097/CJI.0b013e318194a6e8.
46. Levine B.L. Performance-enhancing drugs: design and production of redirected chimeric antigen receptor (CAR) T cells. Cancer Gene Ther 2015;22:79–84. DOI: 10.1038/cgt.2015.5.
47. Kumaresan P., Figliola M., Moyes J.S. et al. Automated cell enrichment of cytomegalovirus-specific T cells for clinical applications using the cytokine-capture system. J Vis Exp 2015;(104). DOI: 10.3791/52808.
48. Wang X., Rivière I. Manufacture of tumorand virus-specific T lymphocytes for adoptive cell therapies. Cancer Gene Ther 2015;22:85–94. DOI: 10.1038/cgt.2014.81.
49. Jensen M.C., Popplewell L., Cooper L.J. et al. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol Blood Marrow Transplant 2010;16(9):1245–56. DOI: 10.1016/j.bbmt.2010.03.014.
50. Kalos M., Levine B.L., Porter D.L. et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011;3(95):95ra73. DOI: 10.1126/scitranslmed.3002842.
51. Savoldo B., Ramos C.A., Liu E. et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 2011;121(5):1822–6. DOI: 10.1172/JCI46110.
52. Till B.G., Jensen M.C., Wang J. et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 2008;112(6):2261–71. DOI: 10.1182/blood-2007-12-128843.
53. Brentjens R.J., Riviere I., Park J.H. et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 2011;118(18):4817–28. DOI: 10.1182/blood-2011-04-348540.
54. Porter D.L., Levine B.L., Kalos M. et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011;365(8):725–33. DOI: 10.1056/NEJMoa1103849.
55. Kochenderfer J.N., Dudley M.E., Feldman S.A. et al. B-cell depletion and remissions of malignancy along with cytokineassociated toxicity in a clinical trial of antiCD19 chimeric-antigen-receptortransduced T cells. Blood 2012;119(12):2709–20. DOI: 10.1182/blood-2011-10-384388.
56. Brentjens R.J., Latouche J.B., Santos E. et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat Med 2003;9(3):279–86. DOI: 10.1038/nm827.
57. Imai C., Mihara K., Andreansky M. et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia 2004;18(4):676–84. DOI: 10.1038/sj.leu.2403302.
58. Sadelain M. CAR therapy: the CD19 paradigm. J Clin Invest 2015;125(9):3392–400. DOI: 10.1172/JCI80010.
59. Porter D.L., Hwang W.T., Frey N.V. et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 2015;7(303):303ra139. DOI: 10.1126/scitranslmed.aac5415.
60. Kochenderfer J.N., Somerville R., Lu L. et al. Anti-CD19 CAR T cells administered after low-dose chemotherapy can induce remissions of chemotherapy-refractory diffuse large B-cell lymphoma. Blood 2014;124(21):550.
61. Turtle C.J., Berger C., Sommermeyer D. et al. Anti-CD19 chimeric antigen receptormodified T cell therapy for B cell nonHodgkin lymphoma and chronic lymphocytic leukemia: fludarabine and cyclophosphamide lymphodepletion improves in vivo expansion and persistence of CAR-T cells and clinical outcomes. Blood 2015;126(23):184.
62. Schuster S.J., Svoboda J., Dwivedy Nasta S. et al. Sustained remissions following chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas. Blood 2015;126(23):183.
63. Fraietta J.A., Beckwith K.A., Patel P.R. et al. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood 2016;127(9):1117–27. DOI: 10.1182/blood-2015-11-679134.
64. Davila M.L., Riviere I., Wang X. et al. Efficacy and toxicity management of 19–28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014;6(224):224ra25. DOI: 10.1126/scitranslmed.3008226.
65. Brentjens R.J., Davila M.L., Riviere I. et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013;5(177):177ra38. DOI: 10.1126/scitranslmed.3005930.
66. Maude S.L., Frey N., Shaw P.A. et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014;371(16):1507–17. DOI: 10.1056/NEJMoa1407222.
67. Grupp S.A., Kalos M., Barrett D. et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013;368(16):1509–18. DOI: 10.1056/NEJMoa1215134.
68. Lee D.W., Kochenderfer J.N., Stetler-Stevenson M. 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(9967):517–28. DOI: 10.1016/S0140-6736(14)61403-3.
69. Garfall A.L., Maus M.V., Hwang W.T. et al. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. N Engl J Med 2015;3736:1040–7. DOI: 10.1056/NEJMoa1504542.
70. Danhof S., Gogishvili T., Koch S. et al. CAR-Engineered T Cells Specific for the Elotuzumab Target SLAMF7 Eliminate Primary Myeloma Cells and Confer Selective Fratricide of SLAMF7+ Normal Lymphocyte Subsets. Blood 2015;126:115.
71. Lonial S., Dimopoulos M., Palumbo A. et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med 2015;373(7):621–31. DOI: 10.1056/NEJMoa1505654.
72. Ali S.A., Shi V., Wang M.L. et al. Remissions of Multiple Myeloma during a Firstin-Humans Clinical Trial of T Cells Expressing an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor; ASH Annual Meeting, 2015: Late-Breaking Abstracts, p. LBA-1.
73. Ryan M.C., Hering M., Peckham D. et al. Antibody targeting of B-cell maturation antigen on malignant plasma cells. Mol Cancer Ther 2007;6:3009–18. DOI: 10.1158/1535-7163.MCT-07-0464.
74. Ramadoss N.S., Schulman A.D., Choi S.H. et al. An anti-B cell maturation antigen bispecific antibody for multiple myeloma. J Am Chem Soc 2015;137:5288–91. DOI: 10.1021/jacs.5b01876.
75. Geyer M.B., Brentjens R.J. Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Cytotherapy 2016;18(11):1393–409. DOI: 10.1016/j.jcyt.2016.07.003.
76. Ahmed N., Brawley V.S., Hegde M. et al. Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma. J Clin Oncol 2015;33:1688–96. DOI: 10.1200/JCO.2014.58.0225.
77. Newick K., O'Brien S., Moon E., Albelda S.M. CAR T-cell therapy for solid tumors. Annu Rev Med 2017;68:139–52. DOI: 10.1146/annurev-med-062315-120245.
78. Fesnak A.D., June C.H., Levine B.L. Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer 2016;16(9):566–81. DOI: 10.1038/nrc.2016.97.
79. Bonifant C.L., Jackson H.J., Brentjens R.J., Curran K.J. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics 2016;3:16011. DOI:10.1038/mto.2016.11.
80. Wing M.G., Moreau T., Greenwood J. et al. Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/ CD18 (LFA-1) on NK cells. J Clin Invest 1996;98(12):2819–26 DOI: 10.1172/JCI119110.
81. Suntharalingam G., Perry M.R., Ward S. et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 2006;355(10):1018–28. DOI: 10.1056/NEJMoa063842.
82. Teachey D.T., Rheingold S.R., Maude S.L. et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013;121(26):5154–7. DOI: 10.1182/blood-2013-02-485623.
83. Morgan R.A., Yang J.C., Kitano M. et al. 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(4):843–51. DOI: 10.1038/mt.2010.24.
84. Brentjens R., Yeh R., Bernal Y. et al. Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. Mol Ther 2010;18(4):666–8. DOI: 10.1038/mt.2010.31.
85. Lee D.W., Gardner R., Porter D.L. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014;124:188–95. DOI:10.1182/blood-2014-05-552729.
86. Grupp S.A., Porter D.L., Teachey D. 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). 54th ASH Annual Meeting and Exposition; Atlanta, GA. 2012. Abstract 2604.
87. Dai H., Wang Y., Lu X., Han W. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy. J Natl Cancer Inst 2016 Jan 27;108(7):djv439. DOI: 10.1093/jnci/djv439.
88. Zhang H., Ye Z. L., Yuan Z.G. et al. New Strategies for the Treatment of Solid Tumors with CAR-T Cells. Int J Biol Sci 2016;12(6):718–29. DOI:10.7150/ijbs.14405.
89. Jones B.S., Lamb L.S., Goldman F., Di Stasi A. Improving the safety of cell therapy products by suicide gene transfer. Front Pharmacol 2014;5:254. DOI: 10.3389/fphar.2014.00254.
90. Gargett T., Brown M.P. The inducible caspase-9 suicide gene system as a “safety switch” to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol 2014;5:235. DOI: 10.3389/fphar.2014.00235.
91. Ciceri F., Bonini C., Stanghellini M.T. 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. DOI: 10.1016/S1470-2045(09)70074-9.
92. Keu K.V., Witney T.H., Yaghoubi S. et al. Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma. Sci Transl Med 2017;9(373). pii: eaag2196. DOI: 10.1126/scitranslmed.aag2196.
93. Zah E., Lin M.Y., Silva-Benedict A. et al. T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells. Cancer Immunol Res 2016;4(6):498–508. DOI: 10.1158/2326-6066.CIR-15-0231.
94. Hillerdal V., Essand M. Chimeric Antigen Receptor-Engineered T Cells for the Treatment of Metastatic Prostate Cancer. BioDrugs 2015;29:75–89. DOI: 10.1007/s40259-015-0122-9.
95. Hamid O., Robert C., Daud A. et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013;369:134–44. DOI: 10.1056/NEJMoa1305133.
96. Craddock J.A., Lu A., Bear A. et al. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J Immunother 2010;33:780. DOI: 10.1097/CJI.0b013e3181ee6675.
97. Di Stasi A., De Angelis B., Rooney C.M. et al. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 2009;113:6392–402. DOI: 10.1182/blood-2009-03-209650.
98. Chmielewski M., Hombach A.A., Abken H. Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunological reviews. 2014;257:83–90. DOI: 10.1111/imr.12125.
99. Zhang L., Kerkar S.P., Yu Z. et al. Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol Ther 2011;19:751–9. DOI: 10.1038/mt.2010.313
Для цитирования:
Павлова А.А., Масчан М.А., Пономарев В.Б. Адоптивная иммунотерапия генетически модифицированными Т-лимфоцитами, экспрессирующими химерные антигенные рецепторы. Онкогематология. 2017;12(1):17-32. https://doi.org/10.17650/1818-8346-2017-12-1-17-32
For citation:
Pavlova A.А., Maschan M.А., Ponomarev V.B. Adoptitive immunotherapy with genetically engineered T lymphocytes modified to express chimeric antigen receptors. Oncohematology. 2017;12(1):17-32. (In Russ.) https://doi.org/10.17650/1818-8346-2017-12-1-17-32
Просмотров: 974
Послать статью по эл. почте 