摘要
В настоящее время широкое распространение в клинической практике получили препараты, нацеленные на ингибирование иммунных контрольных точек (ИКТ). Однако для значительной группы больных монотерапия ингибитором ИКТ не является эффективной. Одна из причин этого кроется в сложном механизме взаимодействия между рядом белков, являющихся рецепторами и лигандами разных ИКТ, которые одновременно присутствуют на поверхности клетки. Одно из решений этой проблемы — совместное подавление экспрессии нескольких молекул ИКТ. В настоящее время проходят клинические исследования, в которых тестируются комбинации ингибиторов ИКТ. Некоторые из таких комбинаций одобрены для использования в клинической практике. Также в последнее время активно изучаются сигнальные пути, вовлеченные в формирование иммунного ответа в результате трансдукции сигнала через белки ИКТ. Таргетное воздействие на ключевые молекулы этих путей совместно с ингибированием контрольных точек рассматривается в качестве новой стратегии иммунотерапии. В обзоре рассмотрены перспективные мишени иммунотаргетной терапии — PD-1/PD-L1 и TIM-3/Gal-9. Охарактеризованы сигнальные пути, ассоциированные с молекулами этих ИКТ. Проведена оценка потенциальных подходов, основанных на одновременном воздействии на молекулы PD-1, PD-L1, TIM-3, Gal-9 и их сигнальные пути.
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