Фармакотерапия аутоиммунных ревматических заболеваний – от моноклональных антител к CAR-T-клеткам: 20 лет спустя

Аутоиммунитет – патологический процесс, связанный с нарушением иммунологической толерантности к нормальным структурным компонентам организма (аутоантигенам), который ассоциируется с преобладанием активации приобретенного (адаптивного) иммунитета и проявляется гиперпродукцией аутоантител. Системные аутоиммунные ревматические заболевания (САРЗ) относятся к числу наиболее частых и тяжелых нозологических форм этой патологии, связанной с аутоиммунитетом. Проблемы фармакотерапии САРЗ являются предметом интенсивных исследований. В начале XXI века для лечения ревматоидного артрита разработано более 20 генно-инженерных биологических препаратов – моноклональные антитела и рекомбинантные белки, – позволяющих контролировать воспаление, связанное с гиперпродукцией «провоспалительных» цитокинов, применение которых позволило кардинально улучшить результаты фармакотерапии. Однако изучению возможностей фармакотерапии, направленной на селективное подавление «аутоиммунного» компонента патогенеза САРЗ, связанного с неконтролируемой активацией В-клеток и восстановлением иммунологической толерантности к аутоантигенам, посвящено значительно меньше исследований. В спектре препаратов, механизм действия которых связан с подавлением патологической активации В-клеток, ведущее место занимает ритуксимаб (РТМ). Примечательно, что 20 лет назад (в 2004 г.) группа исследователей под руководством профессора J.C. Edwards впервые продемонстрировала эффективность РТМ у пациентов с ревматоидным артритом, и данный препарат вскоре был с успехом репозиционирован для лечения широкого круга САРЗ. Крупное достижение фармакотерапии САРЗ связано с применением CAR (chimeric antigen receptor) Т-клеточной терапии, разработанной для лечения рефрактерных гематологических опухолей. Основным компонентом CAR-Т-клеток является генно-инженерный Т-клеточный рецептор, распознающий антиген-мишень без участия главного комплекса гистосовместимости. Хотя и немногочисленные, но чрезвычайно впечатляющие данные, касающиеся высокой частоты достижения ремиссии, получены в процессе адаптации CD19 CAR-T-клеточной терапии для лечения пациентов с тяжелым течением системной красной волчанки (СКВ) и других САРЗ, рефрактерных к стандартным иммуносупрессивным препаратам. В статье обсуждаются результаты применения CAR-T-клеточной терапии при СКВ и других САРЗ и перспективы дальнейших исследований.

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