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

Roman S. Kalinin; Калинин Р. С.; Alexander G. Gabibov; Габибов А. Г.; Nikolay V. Gnuchev; Гнучев Н. В.; Elena Khurs; Хурс Е. Н.; Vera D. Knorre; Кнорре В. Д.; Stanislav S. Terekhov; Терехов С. С.; Mikhail A. Maschan; Масчан М. А.; Alexandr S. Chernov; Чернов А. С.; Georgij B. Telegin; Телегин Г. Б.; Alexey A. Belogurov; Белогуров А. А.; Anastasiia M. Moysenovich; Мойсенович А. М.; Igor A. Yaroshevich; Ярошевич И. А.; Dmitry V. Volkov; Волков Д. В.; Elena V. Konovalova; Коновалова Е. В.; Alexey Schulga; Шульга А. А.; Valeria M. Ukrainskay; Украинская В. М.; Yuri P. Rubtsov; Рубцов Ю. П.; Victoria O. Shipunova; Шипунова В. О.; Sergey M. Deyev; Деев С. М.

doi:10.31857/S2686738922600972

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

Authors: Kalinin R.S.¹, Gabibov A.G.¹^,2, Gnuchev N.V.³, Khurs E.³, Knorre V.D.¹, Terekhov S.S.¹^,2, Maschan M.A.⁴, Chernov A.S.¹, Telegin G.B.¹, Belogurov A.A.¹^,2, Moysenovich A.M.², Yaroshevich I.A.², Volkov D.V.¹, Konovalova E.V.¹, Schulga A.¹, Ukrainskay V.M.¹^,4, Rubtsov Y.P.¹, Shipunova V.O.¹, Deyev S.M.¹^,5
Affiliations:
1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
2. M.V. Lomonosov Moscow State University
3. Engelhardt Institute of molecular Biology, Russian Academy of Sciences
4. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology
5. National Research University Higher School of Economics
Issue: Vol 510, No 1 (2023)
Pages: 231-235
Section: Articles
URL: https://rjmseer.com/2686-7389/article/view/651101
DOI: https://doi.org/10.31857/S2686738922600972
EDN: https://elibrary.ru/QFANKV
ID: 651101

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Abstract
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Abstract

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.

Keywords

Barnase-barstar interaction, DARPins, CAR T cells, solid tumors

References

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