химерный антигенный рецептор

CAR T-клеточная терапия множественной миеломы по материалам конгрессов ASH-2021 и ASCO-2022

НОВЫЕ ТЕХНОЛОГИИ , ,

С.В. Семочкин1,2

1 МНИОИ им. П.А. Герцена — филиал «НМИЦ радиологии» Минздрава России, 2-й Боткинский пр-д, д. 3, Москва, Российская Федерация, 125284

2 ФГАОУ ВО «РНИМУ им. Н.И. Пирогова» Минздрава России, ул. Островитянова, д. 1, Москва, Российская Федерация, 117997

Для переписки: Сергей Вячеславович Семочкин, д-р мед. наук, профессор, 2-й Боткинский пр-д, д. 3, Москва, Российская Федерация, 125284; e-mail: semochkin_sv@rsmu.ru

Для цитирования: Семочкин С.В. CAR T-клеточная терапия множественной миеломы по материалам конгрессов ASH-2021 и ASCO-2022. Клиническая онкогематология. 2023;16(1):1–13.

DOI: 10.21320/2500-2139-2023-16-1-1-13

РЕФЕРАТ

Современное лечение множественной миеломы (ММ), основанное на применении ингибиторов протеасом, иммуномодулирующих препаратов и моноклональных антител, в определенной степени достигло предела своих возможностей. Несмотря на значительный клинический прогресс, ММ по-прежнему относится к категории хронических неизлечимых заболеваний. Терапия опухоль-специфическими Т-клетками с химерным антигенным рецептором (CAR) представляет собой новый эволюционный шаг, направленный к излечению ММ. В качестве основной мишени CAR T-клеточной терапии ММ в настоящее время рассматривается антиген созревания В-клеток (BCMA). Данный рецептор в основном экспрессируется на поверхности опухолевых плазматических клеток при ММ, а также на В-клетках поздних стадий дифференцировки и нормальных плазматических клетках. В 2021–2022 гг. в США и Европейском союзе были одобрены для клинического применения у пациентов с рецидивами/рефрактерным течением ММ два препарата CAR T-клеток: идекабтаген виклейсел (ide-cel) и цилтакабтаген аутолейсел (cilta-cel). Исследования этих препаратов показали весьма обнадеживающие клинические результаты. Клеточные препараты к другим антигенам (GPRC5D, SLAMF7) находятся на ранних стадиях исследований. Настоящий обзор посвящен последним достижениям в сфере CAR Т-клеточной терапии ММ, представленным на недавних конгрессах ASH-2021 и ASCO-2022. Подробно освещаются результаты исследований KarMMa (ide-cel, II фаза) и CARTITUDE-1 (cilta-cel, IB–II фаза). В обзоре приводятся историческая справка по созданию CAR Т-клеток, данные доклинических и текущих клинических исследований в области ММ, освещаются вопросы возможных причин неудач и перспектив дальнейшего совершенствования данной технологии.

Ключевые слова: CAR T-клеточная терапия, множественная миелома, химерный антигенный рецептор, антиген созревания В-клеток.

Получено: 17 июня 2022 г.

Принято в печать: 2 декабря 2022 г.

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Статистика Plumx русский

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Фармакоэкономический анализ терапии CAR Т-клетками при диффузной В-крупноклеточной лимфоме и В-линейных острых лимфобластных лейкозах

ОБЗОРЫ , , , , , ,

И.В. Грибкова, А.А. Завьялов

ГБУ «НИИ организации здравоохранения и медицинского менеджмента ДЗМ», ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088

Для переписки: Ирина Владимировна Грибкова, канд. биол. наук, ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088; тел.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

Для цитирования: Грибкова И.В., Завьялов А.А. Фармакоэкономический анализ терапии CAR Т-клетками при диффузной В-крупноклеточной лимфоме и В-линейных острых лимфобластных лейкозах. Клиническая онкогематология. 2022;15(2):205–12.

DOI: 10.21320/2500-2139-2022-15-2-205-212

РЕФЕРАТ

Генетически модифицированные Т-лимфоциты с химерными антигенными рецепторами (CAR T-клетки) представляют собой новую стратегию лечения пациентов с рецидивами или рефрактерным течением В-клеточных злокачественных новообразований. В 2017–2018 гг. два препарата CAR T-клеточной терапии: тисагенлеклейсел и аксикабтаген силолейсел — были одобрены Управлением по контролю за качеством пищевых продуктов и лекарственных средств США (FDA) и Европейским агентством по лекарственным средствам (EMA) для клинического применения у пациентов с рефрактерным острым лимфобластным лейкозом и рецидивами/рефрактерными В-клеточными лимфомами. К настоящему времени CAR Т-клеточная терапия все более становится неотъемлемой частью клинической практики благодаря своей высокой эффективности. Однако стоимость этого метода противоопухолевого воздействия чрезвычайно высока. Средняя стоимость тисагенлеклейсела составляет 475 000 долларов США ($), а аксикабтагена силолейсела — 373 000 $. Следует отметить, что это только цены на лекарственные препараты без учета других затрат, связанных с данным методом терапии. В работах 2018–2020 гг. группы исследователей предприняли попытки оценить затраты, связанные с CAR T-клеточной терапией. Цель настоящего обзора — анализ этих исследований, оценка общей стоимости терапии и структуры затрат, рассмотрение факторов, ведущих к увеличению затрат, обсуждение возможности повышения доступности технологии CAR-T в целом. Результаты показали, что в среднем общая стоимость терапии тисагенлеклейселом при В-клеточной лимфоме составила 515 150 $, аксикабтагеном силолейселом — 503 955 $. Стоимость терапии острого лимфобластного лейкоза составила 580 459 $. Основными факторами, влияющими на общую стоимость лечения, были цены на препараты CAR T-клеток, высокая степень тяжести нежелательных явлений и большая опухолевая нагрузка до инфузии CAR T-клеточного продукта. Признается, что в качестве основных возможностей повышения доступности терапии CAR T-клетками может служить понижение цены на препараты (например, за счет собственного производства на базе медицинского учреждения), дальнейшее совершенствование терапии с целью снизить ее токсичность, а также применение на ранних стадиях опухолевого заболевания.

Ключевые слова: В-клеточная лимфома, острый лимфобластный лейкоз, CAR T-клеточная терапия, химерный антигенный рецептор, тисагенлеклейсел, аксикабтаген силолейсел, затраты, обзор.

Получено: 29 октября 2021 г.

Принято в печать: 15 февраля 2022 г.

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Статистика Plumx русский

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CAR Т-клетки для лечения хронического лимфоцитарного лейкоза: обзор литературы

ОБЗОРЫ , , ,

И.В. Грибкова, А.А. Завьялов

ГБУ «НИИ организации здравоохранения и медицинского менеджмента ДЗМ», ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088

Для переписки: Ирина Владимировна Грибкова, канд. биол. наук, ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088; тел.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

Для цитирования: Грибкова И.В., Завьялов А.А. CAR Т-клетки для лечения хронического лимфоцитарного лейкоза: обзор литературы. Клиническая онкогематология. 2021;14(2):225–30.

DOI: 10.21320/2500-2139-2021-14-2-225-230

РЕФЕРАТ

Хронический лимфоцитарный лейкоз (ХЛЛ) является наиболее распространенным злокачественным лимфоидным заболеванием взрослых. Несмотря на появление новых высокоэффективных таргетных препаратов, прогноз у больных с рецидивами и резистентной формой заболевания остается неблагоприятным. CAR Т-клеточная терапия, предполагающая использование Т-лимфоцитов с химерным антигенным рецептором (CAR), продемонстрировала свою эффективность в лечении ряда онкогематологических заболеваний, таких как В-клеточные неходжкинские лимфомы и острый лимфобластный лейкоз. В настоящем обзоре литературы рассматривается опыт применения CAR Т-клеток для лечения ХЛЛ. Представлены преимущества и недостатки данной технологии, а также проблемы, которые еще предстоит решить для внедрения метода в широкую клиническую практику.

Ключевые слова: хронический лимфоцитарный лейкоз, CAR T-клеточная терапия, химерный антигенный рецептор, адоптивная терапия, иммунотерапия.

Получено: 15 декабря 2020 г.

Принято в печать: 10 марта 2021 г.

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Клеточный препарат с химерным антигенным рецептором NKG2D в CAR T-терапии рецидивов/рефрактерных острых миелоидных лейкозов и миелодиспластического синдрома

ОБЗОРЫ , , ,

К.A. Левчук1, Е.В. Белоцерковская1,2, Д.Ю. Поздняков1, Л.Л. Гиршова1, А.Ю. Зарицкий1, А.В. Петухов1,2,3

1 ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341

2 ФГБУН «Институт цитологии РАН», Тихорецкий пр-т, д. 4, Санкт-Петербург, Российская Федерация, 194064

3 НТУ «Сириус», Олимпийский пр-т, д. 1, Сочи, Российская Федерация, 354340

Для переписки: Ксения Александровна Левчук, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341; e-mail: levchuk_ka@almazovcentre.ru

Для цитирования: Левчук К.A., Белоцерковская Е.В., Поздняков Д.Ю. и др. Клеточный препарат с химерным антигенным рецептором NKG2D в CAR T-терапии рецидивов/рефрактерных острых миелоидных лейкозов и миелодиспластического синдрома. Клиническая онкогематология. 2021;14(1):138–48.

DOI: 10.21320/2500-2139-2021-14-1-138-148 

РЕФЕРАТ

NK-клетки как элементы врожденного иммунитета реализуют ключевые реакции противоопухолевого иммунного ответа. NKG2D — активационный трансмембранный рецептор NK-клеток, ответственный за инициацию цитотоксичности в ответ на связывание специфичных лигандов генетически модифицированных клеток. Селективная экспрессия лигандов NKG2D открывает уникальные перспективы для терапии широкого спектра опухолей. Острые миелоидные лейкозы (ОМЛ) — это злокачественные опухоли системы крови, характеризующиеся высоким риском развития рецидивов. Сложность терапевтической стратегии при ОМЛ создает необходимость поиска новых подходов к элиминации опухоли с применением инновационных генетических конструкций. Имеющиеся к настоящему времени CAR T-клеточные препараты, несущие рецептор NKG2D, успешно изучаются в клинических исследованиях у пациентов с ОМЛ, доказывая свой высокий терапевтический потенциал.

Ключевые слова: острые миелоидные лейкозы, химерный антигенный рецептор, адоптивная терапия, NKG2D, NK-клетки.

Получено: 22 августа 2020 г.

Принято в печать: 5 декабря 2020 г.

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