BARNASE-BARSTAR SPECIFIC INTERACTION REGULATES CAR-T CELLS CYTOTOXIC ACTIVITY TOWARD MALIGNANCY-Reference-Cited by-同舟云学术

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

Published:2023-05-01 Issue:1 Volume:510 Page:231-235
ISSN:2686-7389
Container-title:Доклады Российской академии наук. Науки о жизни
language:
Short-container-title:Doklady Rossijskoj akademii nauk. Nauki o žizni

Author:

Kalinin Roman S.¹,Shipunova Victoria O.¹,Rubtsov Yuri P.¹,Ukrainskay Valeria M.¹²,Schulga Alexey¹,Konovalova Elena V.¹,Volkov Dmitry V.¹,Yaroshevich Igor A.³,Moysenovich Anastasiia M.³,Belogurov Alexey A.¹³,Telegin Georgij B.¹,Chernov Alexandr S.¹,Maschan Mikhail A.²,Terekhov Stanislav S.¹³,Knorre Vera D.¹,Khurs Elena⁴,Gnuchev Nikolay V.⁴,Gabibov Alexander G.¹³,Deyev Sergey M.¹⁵

Affiliation:

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

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

3. M.V. Lomonosov Moscow State University

4. Engelhardt Institute of molecular Biology, Russian Academy of Sciences

5. National Research University Higher School of Economics

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.

Publisher

The Russian Academy of Sciences

Reference21 articles.

1. Weber E.W., Maus M.V., Mackall C.L., The Emerging Landscape of Immune Cell Therapies. Cell. 2020. V. 181. P. 46–62.

2. Stepanov A.V., et al., Autocrine-based selection of ligands for personalized CAR-T therapy of lymphoma. Sci Adv 2018.V. 4. P. eaau4580.

3. Turtle C.J., et al., Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib. J Clin Oncol. 2017. V. 35. P. 3010–3020.

4. Mancikova V., Smida M., Current State of CAR T-Cell Therapy in Chronic Lymphocytic Leukemia. Int J Mol Sci. 2021. V. 22. P. 5536.

5. Калинин Р.С., et al., Молекулярные подходы к безопасной и контролируемой Т-клеточной терапии. Acta Naturae. 2018. Т. 10. С. 16–23.