Oncolytic virotherapy enhances the efficacy of a cancer vaccine by modulating the tumor microenvironment

Abstract

The efficacy of cancer vaccines has been limited by the immunosuppressive tumor microenvironment, which can be alleviated by immune checkpoint inhibitor (ICI) therapy. Here, we tested if oncolytic viruses (OVs), similar to ICI, can also synergize with cancer vaccines by modulating the tumor microenvironment. VSV‐GP, a chimeric vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, is a promising new OV candidate. Here, we show that in mouse B16‐OVA melanoma, combination treatment of VSV‐GP with an ovalbumin (OVA) peptide‐loaded dendritic cell (DC) vaccine (DCVacc) significantly enhanced survival over the single agent therapies, although both DCVacc and DCVacc/VSV‐GP treatments induced comparable levels of OVA‐specific CD8 T cell responses. Virus replication was minimal so that direct viral oncolysis in B16‐OVA did not contribute to this synergism. The strong therapeutic effect of the DCVacc/VSV‐GP combination treatment was associated with high numbers of tumor‐infiltrating, highly activated T cells and the relative reduction of regulatory T cells in treated and contra‐lateral nontreated tumors. Accordingly, depletion of CD8 T cells but not natural killer cells abrogated the therapeutic effect of DCVacc/VSV‐GP supporting the crucial role of CD8 T cells. In addition, a drastic increase in several proinflammatory cytokines was observed in VSV‐GP‐treated tumors. Taken together, OVs, similar to ICI, have the potential to markedly increase the efficacy of cancer vaccines by alleviating local immune suppression in the tumor microenvironment.

Autologous Transplantation Using Donor Leukocytes Loaded Ex Vivo with Oncolytic Myxoma Virus Can Eliminate Residual Multiple Myeloma

“… 30 Oncolytic vesicular stomatitis virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein (VSV-GP) alone or in combination with peptide-loaded DC vaccine (DCVacc) induces a pro-inflammatory response from mouse BL6-ovalbumin (OVA) melanoma tumors characterized by the release of IFN-γ, TNF, IL-6, IL-1α, and IL-β, among others. 31 …”

Oncolytic vaccinia virus reinvigorates peritoneal immunity and cooperates with immune checkpoint inhibitor to suppress peritoneal carcinomatosis in colon cancer

“…29 In this regard, OV is an attractive therapeutic modality that can induce antigenspecific T cell response with the expansion of cytotoxic effector cells. 30 Vaccinia virus, belonging to the poxvirus family, is highly immunogenic and has optimal characteristics that make it feasible for clinical development. 31 32 JX-594 (pexastimogene devacirepvec, Pexa-vec) is an oncolytic vaccinia virus armed with GM-CSF, and it showed promising antitumor efficacies through its oncolytic, antiangiogenic, and immune-stimulating mechanisms, in both preclinical and clinical studies.…”

Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements

“…Furthermore, concomitant use of TAA-specific mAbs with OVT can enhance the antitumor response. However, the small size of OVs genome has made it difficult to encode whole antibodies [ 268 ] Combination of OVT with DC vaccines also improves the efficacy of DC vaccines by altering the TME immunosuppressive conditions [ 269 ]. OVs could be utilized as tumor vaccines in order to enhance the immune responses against established tumors or even prevent tumor recurrence.…”