Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells
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...
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| Format: | Article |
| Language: | Russian |
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Russian Academy of Sciences, Tomsk National Research Medical Center
2019-02-01
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| Series: | Сибирский онкологический журнал |
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| Online Access: | https://www.siboncoj.ru/jour/article/view/958 |
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| author | E. A. Borobova D. V. Antonets E. V. Starostina L. I. Karpenko A. A. Zheravin A. A. Ilyichev S. I. Bazhan |
| author_facet | E. A. Borobova D. V. Antonets E. V. Starostina L. I. Karpenko A. A. Zheravin A. A. Ilyichev S. I. Bazhan |
| author_sort | E. A. Borobova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T01:53:20Z |
| format | Article |
| id | doaj.art-7444f7cbaa894f4eb9ed37fa44013743 |
| institution | Directory Open Access Journal |
| issn | 1814-4861 2312-3168 |
| language | Russian |
| last_indexed | 2024-04-10T01:53:20Z |
| publishDate | 2019-02-01 |
| publisher | Russian Academy of Sciences, Tomsk National Research Medical Center |
| record_format | Article |
| series | Сибирский онкологический журнал |
| spelling | doaj.art-7444f7cbaa894f4eb9ed37fa440137432023-03-13T09:05:52ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682019-02-01181434910.21294/1814-4861-2019-18-1-43-49610Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cellsE. A. Borobova0D. V. Antonets1E. V. Starostina2L. I. Karpenko3A. A. Zheravin4A. A. Ilyichev5S. I. Bazhan6Национальный медицинский исследовательский центр им. академика Е.Н. Мешалкина; Федеральное бюджетное учреждение науки Государственный научный центр вирусологии и биотехнологии «Вектор»Федеральное бюджетное учреждение науки Государственный научный центр вирусологии и биотехнологии «Вектор»Федеральное бюджетное учреждение науки Государственный научный центр вирусологии и биотехнологии «Вектор»Федеральное бюджетное учреждение науки Государственный научный центр вирусологии и биотехнологии «Вектор»Национальный медицинский исследовательский центр им. академика Е.Н. МешалкинаФедеральное бюджетное учреждение науки Государственный научный центр вирусологии и биотехнологии «Вектор»Федеральное бюджетное учреждение науки Государственный научный центр вирусологии и биотехнологии «Вектор»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.https://www.siboncoj.ru/jour/article/view/958меланомаднк-вакцинные конструкциит-клеточные эпитопыполиэпитопные антигеныцитотоксические т-лимфоцитымеланома кожииммуногеныцитотоксическая активностьиммунный ответ |
| spellingShingle | E. A. Borobova D. V. Antonets E. V. Starostina L. I. Karpenko A. A. Zheravin A. A. Ilyichev S. I. Bazhan Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells Сибирский онкологический журнал меланома днк-вакцинные конструкции т-клеточные эпитопы полиэпитопные антигены цитотоксические т-лимфоциты меланома кожи иммуногены цитотоксическая активность иммунный ответ |
| title | Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells |
| title_full | Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells |
| title_fullStr | Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells |
| title_full_unstemmed | Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells |
| title_short | Ability of protein epitope-containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells |
| title_sort | ability of protein epitope containing constructs associated with melanoma to stimulate the cytotoxic activity of peripheral blood mononuclear cells against melanoma cells |
| topic | меланома днк-вакцинные конструкции т-клеточные эпитопы полиэпитопные антигены цитотоксические т-лимфоциты меланома кожи иммуногены цитотоксическая активность иммунный ответ |
| url | https://www.siboncoj.ru/jour/article/view/958 |
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