Обзор клинических испытаний перспективных биспецифических кандидатов в препараты клеточной CAR-T терапии
Актуальность: Терапия CAR-T (Chimeric Antigen Receptor T-Cell) клетками показала себя крайне эффективно в лечении онкогематологических заболеваний. В ключевых клинических испытаниях для лечения CD19-положительных опухолей (ZUMA-1, ZUMA-3, JULIET, TRANSCEND) полный ответ составил 58%, 51%, 40%, и 59%, соответственно. Тем не менее, успеху CAR-T терапии препятствуют две основные нерешённые проблемы: острые побочные эффекты и рецидивы онкологических заболеваний. С целью профилактики рецидивов разрабатываются стратегии модификации CAR-конструкта, улучшения экспансии и персистенции CAR-T клеток в организме. В связи с тем, что зачастую рецидивы развиваются на фоне потери экспрессии целевого антигена опухолевыми клетками, использование стратегии нацеливания на два и более опухолевых антигена может значительно снизить частоту рецидивов. Цель исследования:В данном обзоре собраны и проанализированы результаты клинических испытаний биспецифических CAR-T препаратов, проведено сравнение ключевых показателей клинического ответа перспективных CAR-T кандидатов с одобренными FDA препаратами данной терапии. Материалы и методы:Анализ литературы проводился па материалам баз данных PubMed, Scopus, Web of Science, на сайте международного реестра клинических исследований Национального института здоровья США (ClinicalTrials.gov). Результаты:Небольшая выборка клинических исследований с опубликованными результатами не позволила нам найти достоверные отличия по основным показателям CAR-T терапии. Тем не менее, выявлена тенденция к увеличению безрецидивной выживаемости пациентов при использовании биспецифических вариантов CAR-T по сравнению с монопрепаратами. Безрецидивная выживаемость составила 61-90% для CD19/CD20 и 40-85% для CD19/CD22 и 44-61% для моноспецифической анти-CD19 CAR-T терапии. Заключение:Рецидивы онкологического заболевания после CAR-T терапии часто возникают вследствие потери антигена опухолевыми клетками, результаты клинических исследований показывают, что стратегия нацеливания препаратов клеточной терапии на два и более антигена может стать эффективной для снижения риска рецидивов, не вызывая при этом ухудшения показателей иммуно- и нейротоксичности препаратов
Сагъдеева АР, Арслан ЛА, Рыбалов АА, и др. Обзор клинических испытаний перспективных биспецифических кандидатов в препараты клеточной CAR-T терапии. Научные результаты биомедицинских исследований. 2025;11(3):451-475. [Sagdeeva AR, Arslan LA, Rybalov AA, et al. Review of clinical trials of promising bispecific candidates for CAR-T cell therapy. Research Results in Biomedicine. 2025;11(3):451-475. Russian].
DOI:10.18413/2658-6533-2025-11-3-0-4
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Работа выполнена в рамках Программы стратегического академического лидерства (ПРИОРИТЕТ-2030) Казанского (Приволжского) федерального университета