BARNASE-BARSTAR SPECIFIC INTERACTION REGULATES CAR-T CELLS CYTOTOXIC ACTIVITY TOWARD MALIGNANCY

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Resumo

The development of CAR-T specific therapy made a revolution in modern oncology. Despite the pronounced therapeutic effects, this novel approach displayed several crucial limitations caused by the complications in pharmacokinetics and pharmacodynamics controls. The presence of the several severe medical complications of CAR-T therapy initiated a set of attempts aimed to regulate their activity in vivo. We propose to apply the barnase-barstar system to control the cytotoxic antitumor activity of CAR-T cells. To menage the regulation targeting effect of the system we propose to use barstar-modified CAR -T cells together with barnase-based molecules. Barnase was fused with designed ankyrin repeat proteins (DARPins) specific to tumor antigens HER2 (human epidermal growth factor receptor 2) The application of the system demonstrates the pronounced regulatory effects of CAR-T targeting.

Sobre autores

Roman Kalinin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Autor responsável pela correspondência
Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Alexander Gabibov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; M.V. Lomonosov Moscow State University

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow

Nikolay Gnuchev

Engelhardt Institute of molecular Biology, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Elena Khurs

Engelhardt Institute of molecular Biology, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Vera Knorre

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Stanislav Terekhov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; M.V. Lomonosov Moscow State University

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow

Mikhail Maschan

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Alexandr Chernov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Georgij Telegin

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Alexey Belogurov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; M.V. Lomonosov Moscow State University

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow

Anastasiia Moysenovich

M.V. Lomonosov Moscow State University

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Igor Yaroshevich

M.V. Lomonosov Moscow State University

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Dmitry Volkov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Elena Konovalova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Alexey Schulga

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Valeria Ukrainskay

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow

Yuri Rubtsov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Victoria Shipunova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow

Sergey Deyev

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; National Research University Higher School of Economics

Email: Roman.Kalinin.93@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow

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