Современные Т-клеточные технологии иммунотерапии солидных опухолей

Согласно принятой концепции иммуноредактирования, взаимодействие клеток злокачественной опухоли и иммунитета представляет собой сложный многофакторный процесс, результатом которого может быть как противоопухолевая эффекторная активность, так и развитие супрессорных механизмов, способствующих опухолевому росту. Накопление научных сведений в области изучения процессов противоопухолевого иммунного ответа и толерантности привело к появлению множества исследовательских и терапевтических подходов, использующих разные звенья иммунной системы для борьбы с неопластическими процессами. Особняком среди имеющихся подходов стоят стратегии, использующие потенциал основных эффекторов адаптивного иммунитета – антигенспецифичных Т-лимфоцитов – для борьбы со злокачественными новообразованиями, появившиеся более века назад и легшие в основу исследований в области иммунотерапии рака. Одним из свидетельств значительного потенциала противоопухолевой активности Т-клеток при использовании в иммунотерапевтических схемах лечения онкологических заболеваний стал успех в терапии гематологических онкологических заболеваний, достичь которого удалось в конце минувшего десятилетия. При этом, однако, терапия солидных злокачественных новообразований по сей день сталкивается с существенными сложностями, ограничивающими эффективность лечения. В этой связи основной задачей обзора является аккумулирование актуальных сведений относительно успехов и ограничений Т-клеточной иммунотерапии в отношении солидных опухолей.

На сегодняшний день фенотип и функционал Т-клеток исследуется и модулируется как в отношении усиления противоопухолевой цитотоксичности, повышения жизнеспособности и пролиферативной активности Т-клеток, так и в отношении преодоления супрессорного влияния опухоли и ее толерогенного окружения на Т-клетки, а также обеспечения направленной миграции эффекторных Т-лимфоцитов в ткани солидных опухолей. В настоящем обзоре рассматриваются иммунотерапевтические подходы, использующие потенциал эффекторных Т-лимфоцитов, существующие на сегодняшний день в виде клинических исследований или применяемых терапевтических схем лечения солидных злокачественных новообразований. Обсуждаются антиген-независимые подходы, направленные на неспецифическое усиление Т-клеточного ответа, такие как терапия рекомбинантными цитоки нами и ингибирование checkpoint-молекул, а также антиген-зависимые, или антиген-специфичные, подходы, такие как адоптивная Т-клеточная терапия эндогенными Т-лимфоцитами или Т-клетками с модифицированным антиген-распознающим рецептором (CAR-T-клетки, TCR-T-клетки), а также использование биспецифических антител в качестве Т-клеточных активаторов. В обзоре описаны преимущества и недостатки каждого из подходов в монотерапии и существующие на сегодняшний день результаты и перспективы их комбинирования друг с другом.

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