Применение T-клеток с химерным антигенным рецептором (CAR-T) в комбинации с химио- и лучевой терапией для лечения солидных опухолей

Терапия онкогематологических заболеваний на основе Т-клеток с химерным антигенным рецептором (chimeric antigen receptor, CAR) открыла новую эру в борьбе с раком крови. Результаты применения клеточной терапии оказались настолько перспективными, что на рынке уже появились 7 коммерческих препаратов для ее проведения. Однако CAR-T-терапия при солидных опухолях оказалась не очень эффективной. К тому же возник ряд проблем, таких как антигенная гетерогенность данных опухолей, иммуносупрессивное микроокружение, слабая инфильтрация опухоли иммунными клетками, истощение и снижение пролиферативной активности и цитотоксичности CAR-T-клеток внутри опухоли, ускользание целевого антигена опухоли, токсичность терапии. Для их решения предпринимаются усилия, направленные на совершенствование и улучшение методики лечения солидных опухолей. Химиотерапия является стандартом лечения большого количества злокачественных новообразований. ее также применяют перед началом клеточной терапии для лимфодеплеции и лучшего приживления вводимых CAR-T-клеток. Показано, что химиотерапия может снижать иммуносупрессивное воздействие опухолевого микроокружения, разрушать строму и способствовать лучшей инфильтрации опухоли СAR-T-клетками, улучшая их выживаемость, персистенцию и цитотоксичность, а также влияя на метаболизм иммунных клеток внутри опухоли. Однако эффективность комбинированного применения ХТ и CAR-T-клеточной терапии зависит от многих факторов: типа опухоли, дозы и схемы лечения, популяции CAR-T-клеток и индивидуальных особенностей организма. Аналогично обстоят дела и с лучевой терапией, которая может как повышать чувствительность опухоли к лечению, так и способствовать выживаемости опухолевых клеток.

В этом обзоре рассматривается применение CAR-T-терапии при солидных опухолях, затрагиваются основные проблемы лечения данных новообразований, пути их решения, а также вопросы возможности использования комбинированного подхода для улучшения эффективности клеточной терапии.

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