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Преодоление иммунной толерантности как способ лечения злокачественных опухолей: новые перспективы
Преодоление иммунной толерантности как способ лечения злокачественных опухолей: новые перспективы
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Аннотация
В настоящем обзоре литературы изложены современные представления о механизмах противоопухолевого иммунитета, а также роли одного из классов новых иммуномодуляторов – блокаторов иммунных регуляторных молекул CTLA4, которые в ближайшее время могут оказаться в арсенале практикующих онкологов России и уже с успехом применяются для лечения диссеминированной меланомы кожи в странах Европы и США. Ипилимумаб – первый препарат, представитель класса, зарегистрированный по данному показанию в странах Европы и США. Принципиально отличающийся от цитостатических препаратов механизм действия обусловливает необходимость других подходов к оценке объективного ответа на лечение и особого внимания к разнообразным, иногда неожиданным для химиотерапевтов побочным реакциям.
Ключевые слова: иммуноонкология, анти-CTLA4, анти-PD1, противоопухолевый иммунитет, ипилимумаб, меланома кожи.
Key words: immuno-oncology, anti-CTLA4, anti-PD1, antitumor immunity, Ipilimumab, cutaneous melanoma.
Ключевые слова: иммуноонкология, анти-CTLA4, анти-PD1, противоопухолевый иммунитет, ипилимумаб, меланома кожи.
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Key words: immuno-oncology, anti-CTLA4, anti-PD1, antitumor immunity, Ipilimumab, cutaneous melanoma.
Полный текст
Список литературы
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15. Wilson KS, Kotb R. Is tremelimumab beneficial in advanced melanoma? J Clin Oncol 2013. 31 (22): 2835–6.
16. Hodi FS et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363 (8): 711–23.
17. Robert C et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364 (26): 2517–26.
18. Wolchok JD et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15 (23): 7412–20.
19. McDermott D et al. Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). Ann Oncol 2013; 24 (10): 2694–8.
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22. Sherrill B et al. Q-TWiST analysis comparing ipilimumab/dacarbazine vs placebo/dacarbazine for patients with stage III/IV melanoma. Br J Cancer 2013; 109 (1): 8–13.
23. Gilardi L et al. Ipilimumab-Induced Immunomediated Adverse Events: Possible Pitfalls in 18F-FDG PET/CT Interpretation. Clin Nucl Med 2013.
24. Kaehler KC et al. Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. Semin Oncol 2010; 37 (5): 485–98.
25. Delyon J et al. Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival. Ann Oncol 2013; 24 (6): 1697–703.
26. Di Giacomo AM et al. Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme. Cancer Immunol Immunother 2013; 62 (6): 1021–8.
27. Holmgaard RB et al. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med 2013; 210 (7): 1389–402.
28. Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol 2008; 8 (1): 74–80.
29. Weber JS et al. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer 2013; 119 (9): 1675–82.
30. Hamid O et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369 (2): 134–44.
31. Wolchok JD et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369 (2): 122–33.
32. Hodi FS, Powels T, Cassier P. Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC). Additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1). Ann Oncol: p. Poster 879 ESMO 2013.
33. GM-CSF/Ipilimumab combination extends melanoma survival. Cancer Discov 2013; 3 (7): OF6.
34. Rosenblatt J et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother 2011; 34 (5): 409–18.
35. Wehler TC et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines. Blood 2007; 109 (1): 365–73.
36. Rosenberg SA et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 2011; 17 (13): 4550–7.
2. Villasor RP, Fetalino MS, Ramirez AT. The Clinical Use of Bcg Vaccine in Stimulating Host Resistance to Cancer. Philipp J Surg Surg Spec 1963; 18: 85–93.
3. Robinson MR. BCG in the management of superficial bladder cancer. Prog Clin Biol Res 1985; 185B: 161–6.
4. Burnet M. Cancer; a biological approach. I. The processes of control. Br Med J 1957; 1 (5022): 779–86.
5. Dunn GP et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3 (11): 991–8.
6. Vesely MD, Schreiber RD. Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy. Ann N Y Acad Sci 2013; 1284: 1–5.
7. Dariavach P et al. Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. Eur J Immunol 1988; 18 (12): 1901–5.
8. Ott PA, Hodi FS, Robert C. CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic modalities with durable clinical benefit in melanoma patients. Clin Cancer Res 2013; 19 (19): 5300–9.
9. Matzinger P. An innate sense of danger. Ann N Y Acad Sci 2002; 961: 341–2.
10. Ribas A, Butterfield LH, Economou JS. Genetic immunotherapy for cancer. Oncologist 2000; 5 (2): 87–98.
11. Van Wijk F et al. The CD28/CTLA-4-B7 signaling pathway is involved in both allergic sensitization and tolerance induction to orally administered peanut proteins. J Immunol 2007; 178 (11): 6894–900.
12. Reuben JM et al. Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in patients with advanced malignant melanoma. Cancer 2006; 106 (11): 2437–44.
13. Ribas A et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol 2013; 31 (5): 616–22.
14. Pfizer stops Ph III trial of single-agent tremelimumab in advanced melanoma. 07.04.2008; 24.11.2013. Available from: http://www.thepharmaletter.com/article/pfizer-stops-ph-iii-trial-of-single-agent-tremelimumab-in-adv....
15. Wilson KS, Kotb R. Is tremelimumab beneficial in advanced melanoma? J Clin Oncol 2013. 31 (22): 2835–6.
16. Hodi FS et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363 (8): 711–23.
17. Robert C et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364 (26): 2517–26.
18. Wolchok JD et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15 (23): 7412–20.
19. McDermott D et al. Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). Ann Oncol 2013; 24 (10): 2694–8.
20. Maio M. Survival amalysis with 5 years of follow up in phase III study of ipilimumab and dacarbazine in metastatic melanoma: ESMO oral presentation 3704. Eur J Cancer 2013.
21. Wolchok JD et al. Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials. Ann Oncol 2013; 24 (8): 2174–80.
22. Sherrill B et al. Q-TWiST analysis comparing ipilimumab/dacarbazine vs placebo/dacarbazine for patients with stage III/IV melanoma. Br J Cancer 2013; 109 (1): 8–13.
23. Gilardi L et al. Ipilimumab-Induced Immunomediated Adverse Events: Possible Pitfalls in 18F-FDG PET/CT Interpretation. Clin Nucl Med 2013.
24. Kaehler KC et al. Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. Semin Oncol 2010; 37 (5): 485–98.
25. Delyon J et al. Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival. Ann Oncol 2013; 24 (6): 1697–703.
26. Di Giacomo AM et al. Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme. Cancer Immunol Immunother 2013; 62 (6): 1021–8.
27. Holmgaard RB et al. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med 2013; 210 (7): 1389–402.
28. Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol 2008; 8 (1): 74–80.
29. Weber JS et al. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma. Cancer 2013; 119 (9): 1675–82.
30. Hamid O et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369 (2): 134–44.
31. Wolchok JD et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369 (2): 122–33.
32. Hodi FS, Powels T, Cassier P. Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC). Additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1). Ann Oncol: p. Poster 879 ESMO 2013.
33. GM-CSF/Ipilimumab combination extends melanoma survival. Cancer Discov 2013; 3 (7): OF6.
34. Rosenblatt J et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother 2011; 34 (5): 409–18.
35. Wehler TC et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines. Blood 2007; 109 (1): 365–73.
36. Rosenberg SA et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 2011; 17 (13): 4550–7.
Авторы
И.В.Самойленко, Г.Ю.Харкевич, Л.В.Демидов
Отделение биотерапии опухолей ФГБУ РОНЦ им. Н.Н.Блохина РАМН, Москва
Отделение биотерапии опухолей ФГБУ РОНЦ им. Н.Н.Блохина РАМН, Москва
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