Enhanced Antitumor Effect of Oncolytic Virotherapy Combined with mRNA-Encoded Immunoadjuvants in Colorectal Carcinoma (CT26) Tumor Model

The search for effective anti-cancer therapies is one of the most significant goals of modern medicine. The combination of oncolytic viruses (OV) and mRNA immunoadjuvants can significantly improve the outcome or even substitute traditional immunotherapy. In addition to the direct OV-mediated cytotoxic elimination of tumor cells, both OV and mRNA immunoadjuvants can significantly alter the immunosuppressive tumor microenvironment (TME) supporting cancer cells and unleash the immune response against the malignant cells. The present study is aimed at assessing the therapeutic effects of recombinant vesicular stomatitis virus (rVSV) and lipid nanoparticles (LNP) delivering mRNA coding for murine interleukin-12 (mIL12) and granulocyte-macrophage colony-stimulating factor (mGMCSF) (mRNA-LNP) in colorectal carcinoma CT26-induced tumors both as independent therapies and in combination with each other. The results of the in vivo experiment on BALB/c mice demonstrated that rVSV monotherapy did not have a significant effect, with the tumor growth inhibition index (TGII) ranging from 13.7 to 29.8% on days 6–10 after the therapy start. While monotherapy with mRNA-LNP was more effective (TGII of 48.6–53.7%), it was the therapy combining the two approaches (rVSV and mRNA-LNP) that resulted in the highest TGII of 66.7% on day 10. While these results can be further improved by optimizing the experimental design, they show the great potential of combination immunotherapy for the treatment of oncological diseases.