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Development of a Humanized Antibody 5D3Hu against the PRAME Tumor Antigen

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Abstract

The PRAME antigen, which is a significant target for monoclonal antibodies, is a tumor-specific marker that is active at all stages of tumor cell differentiation; it induces a spontaneous T-cell response. In this work, a humanized 5D3Hu antibody was constructed on the basis of the mouse monoclonal antibody 5D3 to the PRAME protein and produced in CHO (Chinese hamster ovary tumor) cells. The 5D3Hu antibody demonstrated high affinity for the antigen (1.4 nM), binding to both recombinant and native PRAME protein; it also had an inhibitory effect on the proliferation of PRAME-positive cell lines. These results allow considering the humanized 5D3Hu antibody as a promising therapeutic agent for the treatment of oncological diseases in which overexpression of the PRAME protein is observed.

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ACKNOWLEDGMENTS

The work was performed using the equipment of the Center for collective use of high-throughput computational resources of Moscow State University.

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2019-1249 of 10.06.2019, unique identifier RFMEFI60418X0204).

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Authors and Affiliations

  1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    M. V. Larina, D. A. Dolgikh, D. S. Balabashin, T. K. Aliev & M. P. Kirpichnikov

  2. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478, Moscow, Russia

    Y. P. Finashutina, N. A. Lyzhko & V. A. Misyurin

  3. Department of Biology, Moscow State University, 119192, Moscow, Russia

    V. N. Novoseletsky, D. A. Dolgikh, A. M. Moysenovich & M. P. Kirpichnikov

  4. Department of Chemistry, Moscow State University, 119192, Moscow, Russia

    O. N. Solopova

  5. Russian Research Center for Molecular Diagnostics and Therapy, 117638, Moscow, Russia

    T. K. Aliev

  6. GeneTechnology LLC, 117437, Moscow, Russia

    A. V. Misyurin

Authors
  1. M. V. Larina
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  2. Y. P. Finashutina
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  5. V. N. Novoseletsky
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  6. D. A. Dolgikh
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  8. A. M. Moysenovich
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  9. D. S. Balabashin
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Correspondence to M. V. Larina.

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This article does not contain any research involving humans or animals as research objects.

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Additional information

Translated by N. Onishchenko

Abbreviations: mAb, monoclonal antibodies; CDR, complementarity determining regions; CH, constant domains of immunoglobulin heavy chains; CHO, Chinese hamster ovary cancer cells; FR, framework regions; PBS, phosphate-buffered saline; PBST, Tween-20 supplemented PBS; PRAME, PReferentially expressed Antigen in MElanoma; VH and VL, variable domains of heavy and light chains of immunoglobulins.

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Larina, M.V., Finashutina, Y.P., Lyzhko, N.A. et al. Development of a Humanized Antibody 5D3Hu against the PRAME Tumor Antigen. Russ J Bioorg Chem 48, 360–371 (2022). https://doi.org/10.1134/S1068162022020133

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