INTERFERON TYPE I-EXPRESSING RECOMBINANT VACCINIA VIRUS AS A PLATFORM FOR SELECTIVE IMMUNOTHERAPY OF GLIOBLASTOMA AND MELANOMA

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.