References

mimmun

Медицинская иммунология

Medical Immunology (Russia)

1563-06252313-741X

SPb RAACI

10.15789/1563-0625-2015-5-395-406

mimmun-919

Research Article

ОБЗОРЫ

REVIEWS

ИММУНОТЕРАПИЯ ОПУХОЛЕЙ, ОСНОВАННАЯ НА БЛОКИРОВКЕ ИММУНОЛОГИЧЕСКИХ КОНТРОЛЬНЫХ «ТОЧЕК» («ЧЕКПОЙНТОВ»)

CANCER IMMUNOTHERAPY BASED ON THE BLOCKADE OF IMMUNE CHECKPOINTS

Боголюбова

А. В.

Bogolyubova

A. V.

Младший научный сотрудник, лаборатория молекулярных механизмов иммунитета ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН; кафедра иммунологии, биологический факультет, ФГБОУ ВПО «Московский государственный университет им. М.В. Ломоносова»:

Адрес для переписки: Боголюбова Аполлинария Васильевна ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН 119991, Россия, Москва, ул. Вавилова, 32. Тел.: 8 (499) 135-99-64. Факс: 8 (499) 135-14-05. E-mail: apollinariya.bogolyubova@gmail.com

Junior Research Associate, Laboratory of Molecular Mechanisms of Immunity, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences; Department of Immunology, Faculty of Biology, Moscow State University;

Address for correspondence: Bogolyubova Apollinariya V. Engelhardt Institute of Molecular Biology of Russian Academy of Sciences 119991, Russian Federation, Moscow, Vavilov str., 32. Phone: 7 (499) 135-99-64. Fax: 7 (499) 135-14-05. E-mail: apollinariya.bogolyubova@gmail.com

apollinariya.bogolyubova@gmail.com

Ефимов

Г. А.

Efimov

G. A.

Кандидат биологических наук, заведующий лабораторией трансплантационной иммунологии, ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ; лаборатория молекулярных механизмов иммунитета ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН

PhD (Biology), Head, Laboratory of Transplantation Immunology, National Research Center for Hematology, Moscow, Russian Federation; Laboratory of Molecular Mechanisms of Immunity, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences

apollinariya.bogolyubova@gmail.com

Друцкая

М. С.

Drutskaya

M. S.

Кандидат биологических наук, старший научный сотрудник лаборатории молекулярных механизмов иммунитета, ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН

PhD (Biology), Senior Research Associate, Laboratory of Molecular Mechanisms of Immunity

apollinariya.bogolyubova@gmail.com

Недоспасов

С. А.

Nedospasov

S. A.

Доктор биологических наук, профессор, заведующий лабораторией молекулярных механизмов иммунитета ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН; кафедра иммунологии, биологический факультет, ФГБОУ ВПО «Московский государственный университет им. М.В. Ломоносова»

PhD, MD (Biology), Professor, Head, Laboratory of Molecular Mechanisms of Immunity, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences; Department of Immunology, Faculty of Biology, Moscow State University

apollinariya.bogolyubova@gmail.com

Институт молекулярной биологии им. В.А. Энгельгардта, Москва; Московский государственный университет им. М.В. ЛомоносоваРоссияEngelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow; Moscow State UniversityRussian Federation

Институт молекулярной биологии им. В.А. Энгельгардта, Москва; Гематологический научный центр, МоскваРоссияEngelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow; National Research Center for Hematology, MoscowRussian Federation

Институт молекулярной биологии им. В.А. Энгельгардта, МоскваРоссияEngelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow;Russian Federation

2015

07102015

175395406

2015

Боголюбова А.В., Ефимов Г.А., Друцкая М.С., Недоспасов С.А.

Bogolyubova A.V., Efimov G.A., Drutskaya M.S., Nedospasov S.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.mimmun.ru/mimmun/article/view/919

Иммунологические контрольные «точки» (ИКТ, англ. Immunological checkpoints) – это система ингибиторных механизмов, которые регулируют активацию иммунного ответа, препятствуя запуску аутоиммунных процессов, а также модулируют его, уменьшая вызванные иммунными клетками повреждения в органах и тканях. Опухолевые клетки могут использовать такие контрольные точки для предотвращения активации опухоль-специфических лимфоцитов, таким образом, приобретая устойчивость к действию иммунной системы. Одним из перспективных методов иммунотерапии опухолей является блокировка ингибирующего сигнала, передающегося через иммунологические контрольные точки, приводящая к реактивации противоопухолевого иммунного ответа. Поскольку большая часть контрольных точек функционирует за счет взаимодействий лиганд-рецептор, одна из стратегий современной противоопухолевой терапии основана на создании терапевтических моноклональных антител, блокирующих лиганд или рецептор, а также растворимых рекомбинантных рецепторов, которые могли бы конкурировать за лиганд и таким образом модулировать передачу сигнала. В последние годы в этом направлении иммунотерапии опухолей получены впечатляющие успехи, однако потенциальной платой за вмешательство в естественные супрессорные механизмы является развитие аутоиммунных реакций.

Immune checkpoints represent the system of inhibitory mechanisms regulating the activation of the immune response, preventing the autoimmune processes and modulating the immune response by decreasing the immune cell-mediated damage of tissues and organs. Tumor cells may utilize these checkpoints to prevent the activation of tumor-specific lymphocytes, thereby acquiring resistance against the immune response. The blockade of inhibitory signal that is transduced in immune checkpoints leading to the reactivation of antitumor immune response is a promising method of tumor immunotherapy. Since the majority of immune checkpoints are based on the ligand-receptor interactions, one of contemporary modalities of anti-tumor therapy is based on the development of ligandor receptor-blocking therapeutic monoclonal antibodies, as well as soluble recombinant receptors capable of competing for a ligand and thereby modulating the signal transduction. In the past few years, this field of tumor immunotherapy experienced an impressive success; however, the potential tradeoff for altering of the natural suppressive mechanisms is the development of the autoimmune reactions.

ракиммунотерапияиммунологические контрольные точкипровоспалительные цитокинымоноклональные антителаиммунология

: сancerimmunotherapyimmune checkpointsproinflammatory cytokinesmonoclonal antibodyimmunology

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