OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press31610.17650/1818-8346-2019-13-4-27-36HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CAREГЕМОБЛАСТОЗЫ: ДИАГНОСТИКА, ЛЕЧЕНИЕ, СОПРОВОДИТЕЛЬНАЯ ТЕРАПИЯCD-19-directed immunotherapy resistance mechanisms of B-precursor acute lymphoblastic leukemiaМеханизмы резистентности В-линейного острого лимфобластного лейкоза при примененииCD19-направленной иммунотерапииhttps://orcid.org/0000-0003-2921-9770GlukhanyukE. V.ГлуханюкЕ. В.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997 Москва, ул. Саморы Машела, 1

https://orcid.org/0000-0003-1616-4408StepanovA. V.СтепановА. В.
Russian Federation

16/10 Miklukho-Maklaya St., Moscow 117997

117997 Москва, ул. Миклухо-Маклая, 16/10

https://orcid.org/0000-0002-0889-6986PopovA. M.ПоповА. М.
Russian Federation

1 Samory Mashela St., Moscow 117997

117997 Москва, ул. Саморы Машела, 1

https://orcid.org/0000-0003-1735-0093MaschanM. A.МасчанМ. А.
Russian Federation

1 Samory Mashela St., Moscow 117997

Михаил Александрович Масчан 

117997 Москва, ул. Саморы Машела, 1

mmaschan@yandex.ruDmitry Rogachev National Research Center of Pediatric Hematology, Oncology and ImmunologyФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава РоссииShemyakin-Ovchinnikov Institute of Bioorganic ChemistryФГБУН «Институт биоорганической химии им. акад. М.М. Шемякина и Ю.А. Овчинникова РАН»03122018134273602012019020120192018https://oncohematology.abvpress.ru/ongm/article/view/316

Immunotherapy is the most rapidly evolving field in clinical malignant hematology. Targeting of the B-lineage surface antigen CD19 in B-lineage acute lymphoblastic leukemia and B-cell lymphoma is a story of great success. Recently two approaches of CD19 immunotargeting were approved for clinical application: CD3 × CD19 bi-specific T-cell engager blinatumomab and CD19 chimeric antigen receptor (CAR) Tcells. Both approaches demonstrated an unprecedented activity in a cohort of patients with relapsed and refractory B-cell leukemia and lymphoma both in the adult and pediatric population. Early clinical research has showed that tumors are able to escape the immunological control and become resistant to the immune attack. Mechanisms of the tumor immune escape are being actively studied and include diverse pathways, such as alternative splicing of CD19 and immunosuppressive tumor microenvironment. Current review briefly summarizes data regarding the mechanisms of CD19-positive leukemia resistance to CD19 immune targeting and discusses potential approaches to overcome it.

наиболее бурно развивающаяся область клинической онкогематологии. Существенные успехи иммунотерапии связаны с таргетированием антигена CD19, экспрессированного на поверхности опухолевых клеток при В-линейном остром лимфобластном лейкозе и В-клеточных лимфомах. CD19-направленная терапия в мире одобрена к клиническому применению в 2 форматах: CD3 × CD19 биспецифичный препарат (блинатумомаб) и аутологичный клеточный продукт CD19 CAR-T-лимфоциты (chimeric antigen receptor T-lymphocyte). Первый опыт клинического применения данных препаратов показал беспрецедентную эффективность в терапии рецидивов и рефрактерных форм В-линейных лейкозов и лимфом у детей и взрослых. Результаты первых исследований также продемонстрировали, что опухоли способны ускользать из-под иммунологического контроля и терять чувствительность к CD19-направленной иммунотерапии. Механизмы ускользания активно изучаются и включают разнообразные биологические пути: от альтернативного сплайсинга изоформ CD19 до иммуносупрессивного микроокружения опухоли. В настоящем обзоре кратко суммированы данные о механизмах резистентности В-линейных опухолей к CD19-направленной иммунотерапии и потенциальных путях ее преодоления.

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