actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2021-6.4.13actabiomedica-2982Research ArticleОНКОЛОГИЯONCOLOGYИммунотерапия злокачественных опухолей, основанная на ингибировании взаимодействия мембранного белка PD-1 и его лигандовImmunotherapy of cancer tumors with inhibition of PD-1 membrane protein and its ligands interactionЧетверяковА. В.ChetveryakovA. V.

 аспирант кафедры госпитальной хирургии 

672000, г. Чита, ул. Горького, 39а, Россия

 Postgraduate at the Department of the Advanced Level Surgery

 Gorkogo str. 39A, Chita 672000, Russian Federation 

yasnogorsk94@gmail.comЦепелевВ. Л.TsepelevV. L.

 доктор медицинских наук, профессор, заведующий кафедрой госпитальной хирургии

672000, г. Чита, ул. Горького, 39а, Россия

 Dr. Sc. (Med.), Professor, Head of the Department of the Advanced Level Surgery

 Gorkogo str. 39A, Chita 672000, Russian Federation 

viktorcepelev@mail.ruФГБОУ ВО «Читинская государственная медицинская академия» Минздрава РоссииChita State Medical Academy20211210202164146159Copyright © Четверяков А.В., Цепелев В.Л., 20212021Четверяков А.В., Цепелев В.Л.Chetveryakov A.V., Tsepelev V.L.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/2982

Открытие рецептора PD-1 японским учёным Тасуку Хондзё и белка CTLA-4 американским иммунологом Джеймсом Эллисоном стало началом изучения новых регуляторных механизмов активации иммунного ответа. Был введён термин «иммунные контрольные точки», обозначающий систему ингибиторных механизмов, к которым относятся вышеуказанные белки. В обзоре представлены сведения литературы о молекулярной характеристике мембранного белка PD-1 (рецептор запрограммированной клеточной гибели 1) и его значении в регуляции иммунитета. Рассмотрены механизмы использования PD-1 опухолевыми клетками для ускользания от иммунного ответа. Открытие иммунных контрольных точек позволило разработать новый вид терапевтического лечения злокачественных новообразований. В обзоре представлены результаты клинических исследований препаратов, блокирующих взаимодействие мембранного белка PD-1 с его лигандами при различных злокачественных опухолях. К таким препаратам относятся ниволумаб, пембролизумаб, авелумаб. Исследования эффективности применения этих препаратов у пациентов с различными локализациями рака проводились в рамках программ CheckMate, KEYNOTE и JAVELIN Solid Tumor. Некоторые исследования продолжаются. В обзоре представлены и проанализированы результаты изучения клинической эффективности применения препаратов у больных с меланомой, раком лёгкого, почечноклеточным раком, колоректальным раком, классической лимфомой Ходжкина, карциномой Меркеля и раком желудка. Отмечены как положительные, так и неубедительные результаты в лечении пациентов. Эти данные позволили выявить перспективные направления применения препаратов при определённых локализациях злокачественного процесса, а также определить дозу и время применения препарата для получения объективного положительного ответа на лечение.

The identification of the PD-1 receptor by Tasuku Honjo and CTLA-4 by James Ellison marked the beginning of the study of new regulatory pathways activating the immune response. The term “immune checkpoints” was introduced to denote the system of inhibitory mechanisms that include these proteins. The review presents the literature data on the molecular characteristics of the membrane protein PD-1 (programmed cell death 1 receptor) and its role in the regulation of immunity. We consider the PD-1 pathways used of by tumor cells to escape the immune response. The discovery of immune checkpoints made it possible to develop a new type of targeting therapy for cancer. The review presents the results of clinical trials of drugs that block the interaction between the PD-1 and its ligands in various types of cancer. These drugs include nivolumab, pembrolizumab, and avelumab. Studies of these drugs efficacy in patients with various types of cancer localization were conducted within the CheckMate, KEYNOTE and JAVELIN Solid Tumor programs, with some research being in progress. We analyze the results of studying the clinical efficacy of the drugs in patients with melanoma, lung cancer, renal cell cancer, colorectal cancer, classical Hodgkin’s lymphoma, Merkel carcinoma and stomach cancer. Both positive and inconclusive results in the treatment of patients are noted. These data made it possible to identify promising directions for the use of the drugs in certain localizations of the malignant process, as well as to determine the dose and time of their use to obtain an objective positive response to treatment.

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