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Siberian journal of oncology

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Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells

https://doi.org/10.21294/1814-4861-2019-18-1-43-49

Abstract

Aim. The aim of the study was to evaluate the ability of pMEL-TCI and pMEL-A0201 DNA-constructs encoding artificial polyepitope melanoma antigens to induce antitumor T cell immune response ex vivo. material and methods. Dendritic cells were obtained from peripheral blood mononuclear cells of HLA-A02:01-positive donors; DCs transfected with target DNA vaccine constructions were co-cultured with autologous T lymphocytes to stimulate anti-tumor effector T cells. Specific activity of ex vivo stimulated PBMC was assessed (1) by their ability to cause lysis of human melanoma Mel Is cells, and (2) by the level of their granzyme-producing activity. A recombinant plasmid encoding the full-length MART-1 melanoma antigen was used as a positive control. results. All DNA vaccine constructions as well as positive control construction were found to be able to stimulate specific anti-tumor immune responses of autologous PBMC ex vivo, and these PBMC were found to induce melanoma Mel Is cells lysis. Both the efficiency of induced cytotoxic responses and the level of granzymes production stimulated with DCs transfected with pMel-A0201 significantly exceeded those stimulated with DCs transfected with either pMel-TCI or with DNA construction encoding the full-length MART-1 protein. The cytotoxicity level correlates with the level of granzyme B production in CD8+ T lymphocytes. conclusion. DNA vaccine constructions encoding artificial polypeptides composed of tumor antigen epitopes can stimulate the antitumor cytotoxic response. This approach can be used as the basis for the development of new methods of immunotherapy for cancer.

About the Authors

E. A. Borobova
E.N. Meshalkin National Medical Research Center; Federal Budgetary Research Institution State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Elena A. Borobova, Reseracher

15, Rechkunovskaya Street, 630055-Novosibirsk;
Koltsovo-630559, Novosibirsk Region



D. V. Antonets
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Denis V. Antonets, PhD, Senior Researcher

Koltsovo-630559, Novosibirsk Region



E. V. Starostina
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Ekaterina V. Starostina, Researcher

Koltsovo-630559, Novosibirsk Region



L. I. Karpenko
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Larisa I. Karpenko, PhD, Head of the Laboratory of recombinant vaccines

Koltsovo-630559, Novosibirsk Region



A. A. Zheravin
E.N. Meshalkin National Medical Research Center
Russian Federation

Alexander A. Zheravin, MD, PhD, Head of Oncology and Radiotherapy Department

15, Rechkunovskaya Street, 630055-Novosibirsk



A. A. Ilyichev
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Alexander A. Ilyichev, PhD, Head of the Department of Bioengineering

Koltsovo-630559, Novosibirsk Region



S. I. Bazhan
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology «Vector»
Russian Federation

Sergei I. Bazhan, PhD, Head of the Theoretical Department

Koltsovo-630559, Novosibirsk Region



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For citations:


Borobova E.A., Antonets D.V., Starostina E.V., Karpenko L.I., Zheravin A.A., Ilyichev A.A., Bazhan S.I. Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells. Siberian journal of oncology. 2019;18(1):43-49. (In Russ.) https://doi.org/10.21294/1814-4861-2019-18-1-43-49

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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)