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Безопасность и риск фармакотерапии

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Ингибиторы контрольных точек иммунного ответа: новые риски нового класса противоопухолевых средств

https://doi.org/10.30895/2312-7821-2020-8-1-9-22

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Аннотация

Введение в клиническую практику ингибиторов иммунных контрольных точек, блокирующих цитотоксический Т-лимфоцит-ассоциированный протеин 4 (CTLA-4), белок запрограммированной клеточной гибели-1 (PD-1) и лиганд рецептора запрограммированной клеточной гибели (PD-L1), позволило улучшить прогноз пациентов со злокачественными новообразованиями различной локализации. Противоопухолевое действие ингибиторов иммунных контрольных точек основано на блокаде сигнальных путей CTLA-4 и PD-1/PD-L1 и усилении противоопухолевой активности лимфоцитов. Однако ингибирование иммунных контрольных точек может приводить к нарушению регуляции иммунных ответов и возникновению нового вида нежелательных реакций, связанных с изменением активности иммунокомпетентных клеток в организме. Цель работы: анализ нежелательных реакций, связанных с применением ингибиторов иммунных контрольных точек. Показано, что структура иммуноопосредованных нежелательных реакций различалась в зависимости от класса ингибиторов иммунных контрольных точек. Частота развития иммуноопосредованных нежелательных реакций была выше при использовании ингибиторов CTLA-4, чем ингибиторов PD-1/PD-L1, и значительно возрастала на фоне комбинированной терапии. При терапии ингибиторами CTLA-4 чаще наблюдались реакции со стороны кожи (сыпь, кожный зуд), желудочно-кишечного тракта (диарея, колит), эндокринных желез (гипофизит). При лечении ингибиторами PD-1 преобладали нарушения со стороны органов дыхания (пневмонит), реже отмечались нарушения со стороны желудочно-кишечного тракта (диарея, колит), кожи (сыпь, зуд) и эндокринных желез (гипотиреоз). Терапия ингибиторами PD-L1 сопровождалась развитием пневмонита. При развитии иммуноопосредованных нежелательных реакций может потребоваться прекращение лечения и введение иммунодепрессантов, в связи с этим ранняя диагностика и своевременная терапия осложнений служат важными критериями успешного проведения противоопухолевой терапии. Дальнейшее изучение механизмов развития иммуноопосредованных нежелательных реакций позволит оптимизировать противоопухолевую терапию ингибиторами иммунных контрольных точек.

Об авторах

Е. В. Шубникова
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия

Шубникова Елена Владимировна, канд. мед. наук

Петровский бульвар, д. 8, стр. 2, Москва, 127051



Т. М. Букатина
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия

Букатина Татьяна Михайловна, канд. мед. наук

Петровский бульвар, д. 8, стр. 2, Москва, 127051



Н. Ю. Вельц
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия

Вельц Наталья Юрьевна, канд. биол. наук, доцент

Петровский бульвар, д. 8, стр. 2, Москва, 127051



Д. А. Каперко
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия

Каперко Дмитрий Алексеевич

Петровский бульвар, д. 8, стр. 2, Москва, 127051



Г. В. Кутехова
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия

Кутехова Галина Викторовна

Петровский бульвар, д. 8, стр. 2, Москва, 127051



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Для цитирования:


Шубникова Е.В., Букатина Т.М., Вельц Н.Ю., Каперко Д.А., Кутехова Г.В. Ингибиторы контрольных точек иммунного ответа: новые риски нового класса противоопухолевых средств. Безопасность и риск фармакотерапии. 2020;8(1):9-22. https://doi.org/10.30895/2312-7821-2020-8-1-9-22

For citation:


Shubnikova E.V., Bukatina T.M., Velts N.Yu., Kaperko D.A., Kutekhova G.V. Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents. Safety and Risk of Pharmacotherapy. 2020;8(1):9-22. (In Russ.) https://doi.org/10.30895/2312-7821-2020-8-1-9-22

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