actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2024-9.5.6actabiomedica-5034Research ArticleБИОЛОГИЯ И МЕДИЦИНСКАЯ БИОЛОГИЯBIOLOGY AND MEDICAL BIOLOGYCAR НК-терапия: методы активации и экспансии НК-клетокCAR natural killer cell therapy: Natural killer cell activation and expansionhttps://orcid.org/0000-0001-7478-8783ФёдороваП. О.FedorovaP. O.

Фёдорова Полина Олеговна – младший научный сотрудник лаборатории прикладной вирусологии, аспирант; лаборант-исследователь лаборатории клеточного иммунитета; ассистент кафедры микробиологии, вирусологии и иммуннологии

105064, г. Москва, Малый Казенный пер., 5А

115522, г. Москва, Каширское шоссе, д. 24

119991, г. Москва, ул. Трубецкая, 8, стр. 2

Polina O. Fedorova – Junior Research Officer at the Laboratory of Applied Virology, Postgraduate; Clinical Research Assistant at the Laboratory of Cell Immunity; Teaching Assistant at the Department of Microbiology, Virology and Immunology

Malyi Kazennyi lane 5A, Moscow 105064

Kashirskoye Highway 24, Moscow 115522

Trubetskaya str. 8-2, Moscow 119991

ppolite@mail.ruФГБНУ «Научно-исследовательский институт вакцин и сывороток им. И.И. Мечникова»; Научно-исследовательский институт экспериментальной диагностики и терапии опухолей, ФГБУ «Научный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России; ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)I.I. Mechnikov Vaccine and Serum Research Institute; Research Institute of Experimental Therapy and Diagnostics of Tumor, N.N. Blokhin National Medical Center of Oncology; I.M. Sechenov First Moscow State Medical University (Sechenov University)202422112024955365Copyright © Фёдорова П.О., 20242024Фёдорова П.О.Fedorova P.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/5034

На сегодняшний день терапия Т-клетками с химерным рецептором антигена (CAR, chimeric antigen receptor) представляет собой эффективный метод лечения в области онкогематологических заболеваний. Однако иммунотерапия на основе Т-лимфоцитов имеет определённые недостатки, ограничивающие область применения данного подхода. Многообещающей альтернативой служит основанная на натуральных киллерах (НК-клетках) CAR-терапия, поскольку она не требует детального подбора донора по системе человеческих лейкоцитарных антигенов; НК-клетки обладают уникальным механизмом распознавания и уничтожения опухолевых клеток. Кроме того, при инфузии натуральные киллеры не вызывают тяжёлых токсических реакций. Создание CAR НК-продукта представляет собой непростую задачу, включающую культивирование клеток, использование методов генной инженерии, а также проверку контроля качества полученного биомедицинского клеточного продукта (БМКП). Для пролиферации и усиления эффекторных функций НК-клеткам требуется наличие в питательной среде интерлейкинов, фидерных клеток или их компонентов и активаторов иммунной системы. В данном обзоре основное внимание уделяется различным подходам к активации и экспансии натуральных киллеров в процессе культивирования, а также затрагиваются вопросы о достоинствах и недостатках выбранного метода терапии и о регуляторных аспектах создания полноценного БМКП.

Currently, chimeric antigen receptor (CAR) T-cell therapy is an effective treatment method of hematological malignancies. However, T-lymphocyte-based immunotherapy has certain limitations for the scope of application of this approach. A promising alternative is CAR therapy based on natural killer (NK) cells, since it does not require detailed donor selection according to the human leukocyte antigen system; NK cells have a unique mechanism for recognizing and destroying tumor cells. In addition, NK cells do not cause severe toxic reactions when infused. The creation of a CAR NK product is a complex task includes cell culturing, using genetic engineering methods, and quality control testing of the resulting biomedical cell product (BMCP). For proliferation and effector function enhancement, NK cells require the presence of interleukins, feeder cells or their components, and immune system activators in the nutrient medium. This review focuses on various approaches to the activation and expansion of natural killer cells during cultivation, and also addresses the issues of the advantages and disadvantages of the chosen therapy and the regulatory aspects of creating a full-fledged BMCP.

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The authors declare that there are no conflicts of interest present.