Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press72710.17650/2313-805X-2024-11-4-23-40REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИImmunotherapy of malignant gliomas: a modern view on the problemИммунотерапия злокачественных глиом: современное состояние проблемыhttps://orcid.org/0000-0002-0134-1005PichuginА. А.ПичугинА. А.
Russian Federation

49 Butlerova St., Kazan 420012

12А Karbyshevа St., Kazan 420101

420012 Казань, ул. Бутлерова, 49

420101 Казань, ул. Карбышева, 12А

https://orcid.org/0000-0002-6165-3668KovyazinaR. R.КовязинаР. Р.
China

8 Duke Avenue, Jiangsu Kunshan 215316

215316 Куньшань, Цзянсу, Дьюк Авеню, 8

https://orcid.org/0000-0002-8046-2533TrondinА.ТрондинА. А.
Spain

Calle del Prof Martín Lagos, S/N, Moncloa – Aravaca, Мадрид 28040

28040 Мадрид, Calle del Prof Martín Lagos, S/N, Moncloa – Aravaca

https://orcid.org/0000-0003-1227-8918AlekseevА. G.АлексеевА. Г.
Russian Federation

49 Butlerova St., Kazan 420012

12А Karbyshevа St., Kazan 420101

420012 Казань, ул. Бутлерова, 49

420101 Казань, ул. Карбышева, 12А

https://orcid.org/0000-0002-2078-4274KopninP. B.КопнинП. Б.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0009-0003-4348-9141GesselT. V.ГессельТ. В.
Russian Federation

49 Butlerova St., Kazan 420012

420012 Казань, ул. Бутлерова, 49

https://orcid.org/0000-0003-2415-1084BoichukS. V.БойчукС. В.
Russian Federation

Sergei Vasilyevich Boichuk

49 Butlerova St., Kazan 420012

Bld. 1, 2/1 Barricadnaya St., Moscow 125993

Сергей Васильевич Бойчук

420012 Казань, ул. Бутлерова, 49

125993 Москва, ул. Баррикадная, 2/1, стр. 1

boichuksergei@mail.ruKazan State Medical University, Ministry of Health of RussiaФГБОУ ВО «Казанский государственный медицинский университет» Минздрава РоссииInterregional Clinical Diagnostic CenterГАУЗ «Межрегиональный клинико-диагностический центр»Duke Kunshan UniversityУниверситет герцога КуньшаняHospital Clínico San CarlosКлиника Сан-КарлосCarcinogenesis Institute of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaНаучно-исследовательский институт канцерогенеза ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииRussian Medical Academy of Continuous Professional EducationФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России1512202411423400912202409122024Copyright ©; 2024, Pichugin А.А., Kovyazina R.R., Trondin А., Alekseev А.G., Kopnin P.B., Gessel T.V., Boichuk S.V.Copyright ©; 2024, Пичугин А.А., Ковязина Р.Р., Трондин А.А., Алексеев А.Г., Копнин П.Б., Гессель Т.В., Бойчук С.В.2024Pichugin А.А., Kovyazina R.R., Trondin А., Alekseev А.G., Kopnin P.B., Gessel T.V., Boichuk S.V.Пичугин А.А., Ковязина Р.Р., Трондин А.А., Алексеев А.Г., Копнин П.Б., Гессель Т.В., Бойчук С.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/727

Malignant gliomas are one of the most common brain tumors in adults arising from glial cells with an extremely poor prognosis. Generally, therapy of malignant gliomas consists of radical surgical removal followed by radio- and/or chemotherapy. However, prognosis of the disease remains unfavorable.The review presents main clinical, morphological and molecular characteristics of gliomas, their prognostic significance and role in the choice of targeted therapy based on using tyrosine kinase inhibitors and/or monoclonal antibodies. The current aspects of immunotherapy of gliomas (i.e., activation of immune cells, or blockage of immunosuppressive signaling) are discussed in detail. One of the well-known approaches of cancer immunotherapy is based on immune checkpoint inhibitors. These drugs might be effective in treatment of malignant gliomas overexpressing the molecules that suppress immune cells functions. Another promising approach of gliomas immunotherapy is based on genetically modified CAR-T cells (CAR – chimeric antigen receptor) which might identify and eliminate cancer cells. Cytokine therapy is also perspective treatment approach, as well as gene therapy which is associated with editing viral genes for production of oncolytic viruses used as anticancer vaccines. Vaccines are being developed to generate the specific antibodies recognized cancer cells and thereby stimulate the immune system to identify and destroy tumor cells.Despite the promising potential of various gliomas immunotherapy methods, most of them are at different stages of preclinical and clinical trials. Some of them demonstrate promising results and good perspective for the further use to treat glioma patients.

Злокачественные глиомы являются наиболее распространенными опухолями из клеток глиального ряда головного мозга у взрослых и характеризуются крайне неблагоприятным прогнозом. Терапия злокачественных глиом, как правило, включает максимально радикальное хирургическое удаление опухоли с последующим проведением лучевой терапии и/или химиотерапии.В обзоре представлены основные клинико-морфологические и молекулярно-генетические характеристики глиом, их прогностическая значимость, а также роль в выборе тактики таргетной терапии с использованием соответствующих ингибиторов тирозинкиназ и моноклональных антител. Особое внимание уделяется современным аспектам в области иммунотерапии злокачественных глиом, таким как активация иммунных клеток и блокирование различных механизмов, используемых опухолью для уклонения от иммунной системы. Одним из наиболее изученных направлений иммунотерапии злокачественных новообразований является применение ингибиторов контрольных точек иммунного ответа. Данные препараты могут быть эффективны в лечении злокачественных глиом, в которых отмечается гиперэкспрессия молекул, оказывающих супрессорное действие на клетки иммунной системы. Еще одним перспективным направлением иммунотерапии является использование генетически модифицированных CAR-T-клеток (CAR – химерный антигенный рецептор), что подразумевает применение модифицированных иммунных клеток, способных распознавать и уничтожать опухолевые клетки. Помимо этого, к перспективным подходам иммунотерапии глиом относят цитокинотерапию и генную терапию, связанную c генным редактированием вирусов для производства онколитических вирусных вакцин. Разрабатываются вакцины, содержащие специфичные для опухолевых клеток антигены, которые могут стимулировать иммунную систему для их распознавания и последующего уничтожения.Несмотря на перспективность иммунотерапии глиом, многие вышеперечисленные иммунотерапевтические подходы к лечению злокачественных глиом находятся на различных стадиях доклинических и клинических исследований, результаты некоторых из которых многообещающие.

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