nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2021-8-2-84-95nodgo-724Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSНовейшие тенденции в совершенствовании CAR-Т-клеточной терапии: от лейкозов к солидным злокачественным новообразованиямThe latest trends in improving CAR-T cell therapy: from leukemia to solid malignant tumorshttps://orcid.org/0000-0001-5758-8552ЕршовА. В.ErshovA. V.

Ершов Антон Валерьевич - доктор медицинских наук, профессор кафедры патофизиологии Первого МГМУ им. И.М. Сеченова, старший научный сотрудник НИИ общей реаниматологии им. В.А. Неговского ФНКЦ РР.

119991, Москва, ул. Трубецкая, 8, стр. 2; 107031, Москва, ул. Петровка, 25, стр. 2.

SPIN-код: 2059-3248

Dr. of Sci. (Med.), Professor at the Department of Pathophysiology I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Senior Researcher V.A. Negovsky Research Institute of General Reanimatology at Federal Scientific and Clinical Center of Reanimatology and Rehabilitation, Ministry of Science and Higher Education of the Russian Federation.

8-2 Trubetskaya St., Moscow, 119991; 25, Build. 2, Petrovka St., Moscow, 107031.

SPIN-code: 2059-3248

salavatprof@mail.ruhttps://orcid.org/0000-0003-1584-4604ДемьяновГ. В.DemyanovG. V.

Студент 4-го курса Первого МГМУ им. И.М. Сеченова.

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

4th year student I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia.

8-2 Trubetskaya St., Moscow, 119991.

gleb.demyanov.2017@mail.ruhttps://orcid.org/0000-0003-1241-0675НасруллаеваД. А.NasrullaevaD. A.

Студентка 4-го курса Первого МГМУ им. И.М. Сеченова.

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

4th year student I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia.

8-2 Trubetskaya St., Moscow, 119991.

diana.nasrullaeva.00@mail.ruhttps://orcid.org/0000-0003-0206-0114РадкевичЕ. Р.RadkevichE. R.

Студентка 4-го курса Первого МГМУ им. И.М. Сеченова.

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

4th year student I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia.

8-2 Trubetskaya St., Moscow, 119991.

lizysha99@mail.ruhttps://orcid.org/0000-0001-9034-4912ДолгихВ. Т.DolgikhV. T.

Доктор медицинских наук, профессор, заслуженный деятель науки РФ, главный научный сотрудник лаборатории клинической патофизиологии критических состояний НИИ общей реаниматологии им. В.А. Неговского ФНКЦ РР.

107031, Москва, ул. Петровка, 25, стр. 2.

SPIN-код: 2052-1445

Dr. of Sci. (Med.), Chief Researcher Laboratory of Clinical Pathophysiology of Critical States V.A. Negovsky Research Institute of General Reanimatology at Federal Scientific and Clinical Center of Reanimatology and Rehabilitation, Ministry of Science and Higher Education of the Russian Federation.

25, Build. 2, Petrovka St., Moscow, 107031.

SPIN-code: 2052-1445

prof_dolgih@mail.ruhttps://orcid.org/0000-0003-3797-5808СидороваН. В.SidorovaN. V.

Заведующая отделением детской трансплантации костного мозга и гемопоэтических стволовых клеток НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 7729-5713

Head of the Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

SPIN-code: 7729-5713

valerevna25@mail.ruhttps://orcid.org/0000-0002-1469-2365ВалиевТ. Т.ValievT. T.

Доктор медицинских наук, Заведующий детским отделением химиотерапии гемобластозов отдела гематологии и трансплантации костного мозга НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 9802-8610

Dr. of Sci. (Med.), Head of the Children's Department of Hemoblastosis Chemotherapy of the Department of Hematology and Bone Marrow Transplantation of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

SPIN-code: 9802-8610

timurvaliev@mail.ruhttps://orcid.org/0000-0002-1925-2457ЕфимоваМ. М.EfimovaM. M.

Врач-детский онколог НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Pediatric Oncologist Research Institute of Pediatric Oncology and Hematology of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

kivi123987@gmail.comhttps://orcid.org/0000-0003-2395-4045МачневаЕ. Б.MachnevaE. B.

Кандидат медицинских наук, врач-гематолог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина, врач-гематолог отделения трансплантации костного мозга Российской детской клинической больницы РНИМУ им. Н.И. Пироговаэ.

115478, Москва, Каширское шоссе, 23; 119571, Москва, Ленинский просп., 117.

SPIN-код: 6143-8644

Cand. of Sci. (Med.), Hematologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, Hematologist Department of Bone Marrow Transplantation at the Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478; 117 Leninskiy Prosp., Moscow, 119571.

SPIN-code: 6143-8644

lena.machneva@yandex.ruhttps://orcid.org/0000-0002-2945-284XКиргизовК. И.KirgizovK. I.

Кандидат медицинских наук, заместитель директора по научной и образовательной работе НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 3803-6370

Cand. of Sci. (Med.), Deputy Director for Scientific and Educational Work of Research Institute of Pediatric Oncology and Hematology at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

SPIN-code: 3803-6370

k.kirgizov@ronc.ruhttps://orcid.org/0000-0002-0132-167XКиселевскийМ. В.KiselevskyM. V.

Доктор медицинских наук, профессор, заведующий лабораторией клеточного иммунитета НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 8687-2387

Dr. of Sci. (Med.), Professor, Head of the Laboratory of Cellular Immunity of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

SPIN-code: 8687-2387

kisele@inbox.ruhttps://orcid.org/0000-0002-3003-4362МанасоваЗ. Ш.ManasovaZ. Sh.

Кандидат медицинских наук, доцент кафедры патофизиологии Первого МГМУ им. И.М. Сеченова.

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

SPIN-код: 2251-6634

Cand. of Sci. (Med.), Associate Professor of the Department of Pathophysiology at I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia.

8-2 Trubetskaya St., Moscow, 119991.

SPIN-code: 2251-6634

zmanasova@yandex.ruПервый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет); НИИ общей реаниматологии имени В.А. Неговского ФГБУН «Федеральный научно-клинический центр реаниматологии и реабилитологии» Министерства науки и высшего образования Российской ФедерацииРоссияI.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University); V.A. Negovsky Research Institute of General Reanimatology, Federal Scientific and Clinical Center of Reanimatology and Rehabilitation, Ministry of Science and Higher Education of the Russian FederationRussian FederationПервый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)Russian FederationНИИ общей реаниматологии имени В.А. Неговского ФГБУН «Федеральный научно-клинический центр реаниматологии и реабилитологии» Министерства науки и высшего образования Российской ФедерацииРоссияV.A. Negovsky Research Institute of General Reanimatology, Federal Scientific and Clinical Center of Reanimatology and Rehabilitation, Ministry of Science and Higher Education of the Russian FederationRussian FederationНМИЦ онкологии им. Н.Н. Блохина Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of RussiaRussian FederationНМИЦ онкологии им. Н.Н. Блохина Минздрава России; РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia; Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussian Federation202112072021828495Copyright © Ершов А.В., Демьянов Г.В., Насруллаева Д.А., Радкевич Е.Р., Долгих В.Т., Сидорова Н.В., Валиев Т.Т., Ефимова М.М., Мачнева Е.Б., Киргизов К.И., Киселевский М.В., Манасова З.Ш., 20212021Ершов А.В., Демьянов Г.В., Насруллаева Д.А., Радкевич Е.Р., Долгих В.Т., Сидорова Н.В., Валиев Т.Т., Ефимова М.М., Мачнева Е.Б., Киргизов К.И., Киселевский М.В., Манасова З.Ш.Ershov A.V., Demyanov G.V., Nasrullaeva D.A., Radkevich E.R., Dolgikh V.T., Sidorova N.V., Valiev T.T., Efimova M.M., Machneva E.B., Kirgizov K.I., Kiselevsky M.V., Manasova Z.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/724

Среди современных подходов к лечению онкологических заболеваний важное место занимает CAR-Т-клеточная терапия с использованием цитотоксических лимфоцитов с химерными антигенными рецепторами. Данный подход зарекомендовал себя как эффективный метод лечения острого лимфобластного лейкоза с экспрессией CD19-антигена. Тем не менее нередки рецидивы заболеваний, а лечение солидных опухолей генетически модифицированными лимфоцитами демонстрирует весьма скромные результаты и сопровождается высокой токсичностью. Однако, несомненно, что CAR-Т-клеточная терапия обладает большим потенциалом в лечении онкологических заболеваний и дальнейшее совершенствование структуры и функций генетически модифицированных лимфоцитов с химерными Т-клеточными рецепторами может значительно увеличить эффективность противоопухолевого лечения.

В обзоре представлены современные данные о структуре химерных лимфоцитов разных поколений и освещены тенденции в совершенствовании CAR-Т-клеточной терапии. Представлена также фундаментальная платформа для формирования идеологии применения CAR-Т-клеток в лечении солидных злокачественных новообразований.

CAR-Т cell therapy with the use of cytotoxic lymphocytes with chimeric antigen receptors occupies an important place among modern approaches to the cancer treatment. This therapy has established itself as an effective method of the treatment of CD19+ acute lymphoblastic leukemia. Nevertheless, the recurrences of the illness are not uncommon; the treatment of solid tumors with genetically engineered lymphocytes shows modest results and it is accompanied by the high toxicity. One thing, however, is certain: CAR-Т cell therapy has great potential in the treatment of cancer and further improving of the structure and functions of genetically engineered lymphocytes with chimeric Т cell receptors help greatly increase the efficiency of antitumor treatment.

The review includes the current data on the structure of chimeric lymphocytes of different generations and the trends in improving CAR-Т cell therapy. It includes also the fundamental platform for formation of ideology of use CAR-Т cells for the treatment of solid malignant tumors.

CAR-Т-клеточная терапияхимерные лимфоцитыхимерный антигенный рецепторлейкозысолидные злокачественные новообразованияCAR-Т cell therapychimeric lymphocyteschimeric antigen receptorleukemiasolid malignant tumorsReferencesПавлова А.А., Масчан М. А., Пономарев В.Б. Адоптивная иммунотерапия генетически модифицированными Т-лимфоцитами, экспрессирующими химерные антигенные рецепторы. Онкогематология 2017;12(1): 17-32. doi: 10.17650/1818-8346-2017-12-1-17-32.Pavlova A.A., Maschan M.A., Ponomarev V.B. Adoptive immunotherapy with genetically engineered Т lymphocytes modified to express chimeric antigen receptors. Onkohematologiya = Oncohematology 2017;12(1):17-32. (In Russ.).Fitzmaurice C., Abate D., Abdulle A.S.M. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017. A Systematic Analysis for the Global Burden of Disease Study. 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The authors declare that there are no conflicts of interest present.