Синдром высвобождения цитокинов после терапии Т-клетками с химерным антигенным рецептором: патофизиология, клинические проявления и новые подходы к лечению

Введение. Внедрение терапии Т-клетками с химерным антигенным рецептором (Chimeric antigen receptor, CAR T) в клиническую практику изменило международные стандарты лечения B-клеточных лейкозов, лимфом и множественной миеломы. Наряду с высокой противоопухолевой активностью CAR T-терапия сопровождается нежелательными явлениями: синдром высвобождения цитокинов (СВЦ), с иммунными клетками ассоциированный нейротоксический синдром (ИКАНС), синдром активации макрофагов (САМ).

Цель — представить данные о механизмах иммунной токсичности CAR T-терапии, ее клинических проявлениях, а также стратегиях профилактики и лечения.

Основные сведения. СВЦ — гипервоспалительное состояние, в основе клинических проявлений которого лежат активация и нарушение проницаемости эндотелия. Генетическая предрасположенность к СВЦ связана с полиморфизмом генов адгезии и активации иммунных клеток. В патогенезе играют роль гиперпродукция цитокинов интерлейкинов 1β, 6, 8, 10, интерферона-γ, снижение экспрессии молекул адгезии эндотелием, гиперпродукция факторов проницаемости, интерстициальный отек органов и их дисфункция. Другие осложнения: ИКАНС и САМ. Терапия СВЦ основывается на применении глюкокортикоидов и антицитокиновой терапии. Значительная доля негативных исходов связана с ИКАНС и САМ. Перспективным направлением лечения является применение антагонистов интерлейкина-1.

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