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Modular lentiviral vector system for chimeric antigen receptor design optimization

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Abstract

The article reports the development of a collection of lentiviral vector constructs enabling time-efficient production and testing of different variants of chimeric antigen receptors (CAR). These artificial surface proteins make it possible to redirect the activity of immune cytotoxic T-cells towards cancer cells. Chimeric antigen receptors usually encompass four functional modules, namely, antigen recognition, flexible linker, transmembrane, and signal modules. The use of modules with different properties allows modulating the affinity and specificity of CAR interaction with target antigens, as well as intensity and quality of activation signaling, which determines the cytotoxic properties of CAR T-cells, as well as their proliferation rate and time of persistence in the organism. The proposed vector system make it possible to easily test various combinations of CAR modules while its being open to distribution allows the direct comparison of the results obtained by different scientific groups.

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Abbreviations

CAR:

chimeric antigen receptor

copGFP:

green fluorescent protein from the copepoda Pontellina plumata

GlucSP:

leader sequence of Gaussia princeps luciferase

MHC:

main histocompatibility complex

mIgk:

leader sequence of the murine immunoglobuline light chain, Igκ

PSCA:

prostate stem cell antigen

PSMA:

prostate-specific membrane antigen

scFv:

single chain variable antibody fragment

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Authors and Affiliations

  1. Institute of Molecular and Cell Biology, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    S. V. Kulemzin, N. A. Chikaev, O. Y. Volkova, V. V. Kuznetsova, A. V. Taranin & A. A. Gorchakov

  2. Novosibirsk State University, Novosibirsk, 630090, Russia

    V. V. Kuznetsova, A. V. Taranin & A. A. Gorchakov

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  1. S. V. Kulemzin
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  2. N. A. Chikaev
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  3. O. Y. Volkova
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Correspondence to A. A. Gorchakov.

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The paper is based on the materials of the “Chemical Biology 2016” conference; Novosibirsk, Russia, July 24–29, 2016.

Original Russian Text © S.V. Kulemzin, N.A. Chikaev, O.Y. Volkova, V.V. Kuznetsova, A.V. Taranin, A.A. Gorchakov, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 2, pp. 124–132.

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Kulemzin, S.V., Chikaev, N.A., Volkova, O.Y. et al. Modular lentiviral vector system for chimeric antigen receptor design optimization. Russ J Bioorg Chem 43, 107–114 (2017). https://doi.org/10.1134/S1068162017020091

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