Copyright: © 2024 by the authors. Licensee: Pirogov University.
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ORIGINAL RESEARCH

Interferon type I-expressing recombinant vaccinia virus as a platform for selective immunotherapy of glioblastoma and melanoma

About authors

1 Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow, Russia

2 Federal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medical Biological Agency of Russia, Moscow, Russia

3 Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency, Moscow, Russia

4 Research Institute of Pulmonology of the Federal Medical Biological Agency, Moscow, Russia

Correspondence should be addressed: Anastasia V. Lipatova
Vavilova, 32/1, Moscow, 119991, Russia; moc.liamg@vnaavotapil

About paper

Funding: the design of recombinant vaccinia virus strains was supported by the Russian Science Foundation grant No. 23-14-00370, and assessment of their properties in in vitro and in vivo models was supported by the Russian Science Foundation grant No. 22-64-00057; histologic and immunohistochemical assessment of tumor tissue was supported by FMBA of Russia.

Author contribution: Naberezhnaya ER — implementation of in vitro and in vivo experiments, manuscript writing; Soboleva AV — flow cytometry data acquisition, determining the cell line sensitivity to viruses; Vorobyev PO — designing recombinant viruses, production of preparative amounts of strains; Vadekhina VV — conducting in vivo experiments; Yusubalieva GM — interpretation of in vivo experimental data, manuscript writing; Isaeva IV — histologic and immunohistochemical assessment; Baklaushev VP — microscopy, describing histology and immunohistochemistry data, preparing a drawing, manuscript writing; Chumakov PM — manuiscript editing; Lipatova AV — study concept, general project management.

Compliance with ethical standards: the in vivo study was approved by the Ethics Committee of the Federal Scientific and Clinical Center of FMBA of Russia (protocol No. 7 dated 06 September 2022) and conducted in accordance with the the Eurasian Economic Commission Board’s guidelines No. 33 dated 14 November 2023 "On the Guidelines for handling laboratory (experimental) animals when conducting preclinical (non-clinical) studies". The number of animals per group was minimized; the subcutaneous tumor size in the groups did not exceed 2000 mm3. In vitro experiments involved the commercially available animal and human cell lines.

Received: 2024-11-26 Accepted: 2024-12-19 Published online: 2024-12-30
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Immunotherapy with oncolytic viruses (OVs) becomes a full-fledged neoadjuvant therapy method in the paradigm of evidence-based medicine for the growing number of cancers. The use of OVs for immunologically “cold” tumors causing minimal immune response and having the clearly immunosuppressive tumor microenvironment is especially relevant. Recombinant OVs carrying the sequences of proteins activating the immune system can be used to stimulate antitumor response. The study aimed to assess oncoselectivity and antitumor activity of the recombinant OV designed based on the LIVP vaccinia virus strain showing expression of human and murine interpheron alpha sequences (hIFNα and mIFNα, respectively). The in vitro experiments showed that the recombinant OVs designed showed oncoselectivity in relation to tumor cell lines of appropriate species. The ability to effectively infect human adenocarcinoma and glioblastoma cell lines was reported for LIVP-hIFNα. LIVP-mIFNα showed selectivity in relation to glioma Gl261 and melanoma B16 in vitro. The in vivo experiment involving the C57Bl/6 mice with subcutaneous melanoma В16 showed the ability of the intravenously administered LIVP-mIFNα to reduce the size of the subcutaneous tumor allograft and increase tumor infiltration with the CD8+ and NK cells. The recombinant virus designed can be a potential platform for the development of oncolytic virotherapy of human melanoma and glioblastoma.

Keywords: interferon, oncolytic viruses, viral oncolysis, recombinant vaccinia virus strains

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