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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/10.15789/1563-0625-MTC-2444</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-2444</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>Современные Т-клеточные технологии иммунотерапии солидных опухолей</article-title><trans-title-group xml:lang="en"><trans-title>Modern T cell technologies for immunotherapy of solid tumors</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузнецова</surname><given-names>М. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuznetsova</surname><given-names>M. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кузнецова М.С. – к.б.н., научный сотрудник лаборатории молекулярной иммунологии</p></bio><bio xml:lang="en"><p>Kuznetsova M.S., PhD (Biology), Research Associate, Laboratory of Molecular Immunology</p><p>Novosibirsk</p></bio><email xlink:type="simple">mskuz92@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шику</surname><given-names>Хироши</given-names></name><name name-style="western" xml:lang="en"><surname>Shiku</surname><given-names>Hiroshi</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шику Хироши – д.м.н., профессор, заведующий лабораторией клеточных технологий иммунотерапии; заведующий кафедрой иммуногенной терапии и персонализированной иммунотерапии рака</p></bio><bio xml:lang="en"><p>Shiku Hiroshi, PhD, MD (Medicine), Professor, Head, Laboratory of Cellular Technologies of Immunotherapy; Head, Department of Immuno-Gene Therapy</p><p>Novosibirsk</p></bio><email xlink:type="simple">shiku@med.mie-u.ac.jp</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Караулов</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Karaulov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Караулов А.В. – д.м.н., профессор, академик РАН, заведующий кафедрой клинической иммунологии и аллергологии</p></bio><bio xml:lang="en"><p>Karaulov A.V., PhD, MD (Medicine), Professor, Full Member,Russian Academy of Sciences, Head, Department of ClinicalImmunology and Allergology</p><p>Moscow</p></bio><email xlink:type="simple">drkaraulov@mail.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сенников</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Sennikov</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сенников С.В. – д.м.н., профессор, заведующий лабораторией молекулярной иммунологии</p><p>630099, Россия, г. Новосибирск, ул. Ядринцевская, 14.Тел.: 8 (383) 222-19-10</p></bio><bio xml:lang="en"><p>Sennikov S.V., PhD, MD (Medicine), Professor, Head, Laboratory of Molecular Immunology</p><p>14 Yadrintsevskaya St., Novosibirsk 630099 Phone: +7 (383) 222-19-10</p></bio><email xlink:type="simple">sennikovsv@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute of Fundamental and Clinical Immunology</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»; Высшая школа медицины Университета Миэ</institution><country>Япония</country></aff><aff xml:lang="en"><institution>Research Institute of Fundamental and Clinical Immunology; Mie University Graduate School of Medicine</institution><country>Japan</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова»&#13;
Министерства здравоохранения РФ (Сеченовский университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I. Sechenov First Moscow State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>05</day><month>04</month><year>2023</year></pub-date><volume>25</volume><issue>2</issue><fpage>271</fpage><lpage>286</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Кузнецова М.С., Шику Х., Караулов А.В., Сенников С.В., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Кузнецова М.С., Шику Х., Караулов А.В., Сенников С.В.</copyright-holder><copyright-holder xml:lang="en">Kuznetsova M.S., Shiku H., Karaulov A.V., Sennikov S.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.mimmun.ru/mimmun/article/view/2444">https://www.mimmun.ru/mimmun/article/view/2444</self-uri><abstract><p>Согласно принятой концепции иммуноредактирования, взаимодействие клеток злокачественной опухоли и иммунитета представляет собой сложный многофакторный процесс, результатом которого может быть как противоопухолевая эффекторная активность, так и развитие супрессорных механизмов, способствующих опухолевому росту. Накопление научных сведений в области изучения процессов противоопухолевого иммунного ответа и толерантности привело к появлению множества исследовательских и терапевтических подходов, использующих разные звенья иммунной системы для борьбы с неопластическими процессами. Особняком среди имеющихся подходов стоят стратегии, использующие потенциал основных эффекторов адаптивного иммунитета – антигенспецифичных Т-лимфоцитов – для борьбы со злокачественными новообразованиями, появившиеся более века назад и легшие в основу исследований в области иммунотерапии рака. Одним из свидетельств значительного потенциала противоопухолевой активности Т-клеток при использовании в иммунотерапевтических схемах лечения онкологических заболеваний стал успех в терапии гематологических онкологических заболеваний, достичь которого удалось в конце минувшего десятилетия. При этом, однако, терапия солидных злокачественных новообразований по сей день сталкивается с существенными сложностями, ограничивающими эффективность лечения. В этой связи основной задачей обзора является аккумулирование актуальных сведений относительно успехов и ограничений Т-клеточной иммунотерапии в отношении солидных опухолей.</p><p>На сегодняшний день фенотип и функционал Т-клеток исследуется и модулируется как в отношении усиления противоопухолевой цитотоксичности, повышения жизнеспособности и пролиферативной активности Т-клеток, так и в отношении преодоления супрессорного влияния опухоли и ее толерогенного окружения на Т-клетки, а также обеспечения направленной миграции эффекторных Т-лимфоцитов в ткани солидных опухолей. В настоящем обзоре рассматриваются иммунотерапевтические подходы, использующие потенциал эффекторных Т-лимфоцитов, существующие на сегодняшний день в виде клинических исследований или применяемых терапевтических схем лечения солидных злокачественных новообразований. Обсуждаются антиген-независимые подходы, направленные на неспецифическое усиление Т-клеточного ответа, такие как терапия рекомбинантными цитоки нами и ингибирование checkpoint-молекул, а также антиген-зависимые, или антиген-специфичные, подходы, такие как адоптивная Т-клеточная терапия эндогенными Т-лимфоцитами или Т-клетками с модифицированным антиген-распознающим рецептором (CAR-T-клетки, TCR-T-клетки), а также использование биспецифических антител в качестве Т-клеточных активаторов. В обзоре описаны преимущества и недостатки каждого из подходов в монотерапии и существующие на сегодняшний день результаты и перспективы их комбинирования друг с другом.</p></abstract><trans-abstract xml:lang="en"><p>According to the common concept of immune editing, the interaction of malignant tumor cells and immune system is a complex multifactorial process, which may result in both antitumor effector activity and development of suppressor mechanisms that promote tumor growth. Accumulation of scientific knowledge in the field of studying the antitumor immune response and tolerance has led to emergence of many research and therapeutic approaches that use different components of the immune system to combat neoplastic processes. Along with currently available approaches, there are strategies that use the potential of antigen-specific T lymphocytes, the main effectors of adaptive immunity, in order to fight malignant neoplasms which appeared more than a century ago and have built the scientific basis of cancer immunotherapy. One line of evidence of the significant antitumor potential of T cells in immunotherapeutic schemes for the cancer treatment was presented by successful therapy of hemato-oncological diseases, achieved at the end of the past decade. At the same time, however, the therapy of solid malignant neoplasms still faces significant difficulties that limit the efficiency of treatment. In this regard, the main objective of the review is to accumulate up-to-date information on the successes and limitations of T cell immunotherapy in the patients with solid tumors. To date, the phenotype and functionality of T cells is being investigated and modulated both towards enhancing antitumor cytotoxicity, increasing viability and proliferative activity of T cells, and in overcoming the immunosuppressive effect of the tumor and its tolerogenic microenvironment upon T cells, as well as ensuring targeted migration of the effector T cells to the malignant tissues. This review discusses immunotherapeutic approaches exploiting the potential of effector T lymphocytes, e.g., current clinical trials or applied therapeutic regimens for the treatment of solid malignant neoplasms. Antigen-independent approaches aimed at nonspecific enhancement of the T cell responses, i.e., therapy with recombinant cytokines and inhibition of immune checkpoint molecules. Antigendependent, or antigen-specific approaches such as adoptive T cell therapy with endogenous T lymphocytes are also discussed as well as trials on T cells with modified antigen-recognition receptor (CAR-Tcells, TCR-Tcells), like as usage of bispecific antibodies as T cell engagers. The review describes the benefits and disadvantages of these approaches in monotherapy, as well as current results and prospects for their mutual combinations.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>иммунотерапия солидных опухолей</kwd><kwd>Т-лимфоциты</kwd><kwd>checkpoint-ингибиторы</kwd><kwd>адоптивная Т-клеточная терапия</kwd><kwd>CAR-T-клетки</kwd><kwd>TCR-T-клетки</kwd><kwd>BiTE-антитела</kwd><kwd>цитокинотерапия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>solid tumors</kwd><kwd>immunotherapy</kwd><kwd>T cells</kwd><kwd>checkpoint inhibitors</kwd><kwd>adoptive T cell therapy</kwd><kwd>CAR-T cells</kwd><kwd>TCR-T cells</kwd><kwd>BiTEantibodies</kwd><kwd>cytokine therapy</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Лежнин Ю.Н., Христиченко А.Ю., Ратникова Н.М., Кравченко Ю.Е., Чумаков С.П. 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