Oncolytic Vaccinia Virus and Anti-PD1-based Combination Therapy Restores Antitumor Immunity in Tumor Microenvironment

N. Badrinath, J. Su-Nam, J. Heo, S.Y. Yoo
Pusan National University,
Korea

Keywords: combination therapy, oncolytic virotherapy, immune checkpoint blockades

Summary:

Tumor microenvironments (TME) consist of various types of regulatory cells, and also limit the therapeutic efficacy of most of the drugs. To overcome these hurdles, immunotherapy-based combination therapies are being developed to modify the immunosuppressive nature of TME and block immune checkpoints on immune cells of tumors. In this study, we used cancer-favour oncolytic vaccinia virus (CVV) and α-PD1 to treat mouse colon cancer. Weekly-based intratumoral injection of CVV and intraperitoneal injection of α-PD1 were tested in subcutaneous CT26 tumor models in Balb/c mice. Tumor volume, survival curve and hemotoxylin and eosin staining, and immunohistochemistry-based analysis indicated benefit of co-treatment received groups, especially simultaneous treatment of CVV and α-PD1.The infiltration of CD8+ T-cells also correlated with these results. Furthermore, PD1 and PD-L1 mRNA expression from these groups confirmed the therapeutic efficacy of this combination therapy. CVV and α-PD1-based combination therapy enhanced tumor infiltrating lymphocytes and also tumor cells killing.