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Elucidating Mechanisms of Antitumor Immunity Mediated by Live Oncolytic Vaccinia and Heat-Inactivated Vaccinia

By Weiyi Wang, Peihong Dai, Shuaitong Liu, Ning Yang, Yi Wang, Rachel A. Giese, Taha Merghoub, Jedd D. Wolchok, Liang Deng

Posted 12 Feb 2021
bioRxiv DOI: 10.1101/2021.02.11.427912

Viral-based immunotherapy has the potential to overcome resistance to immune checkpoint blockade (ICB) and to fill the unmet needs of many cancer patients. Whether or not viral replication and viral-mediated oncolysis are important for oncolytic vaccinia virus-induced antitumor effects remains unclear. Here we compared the antitumor effects of live vaccinia virus expressing murine granulocyte-macrophage colony-stimulating factor (OV-GM) versus its heat-inactivated version (Heat-iOV-GM). We find that intratumoral injection live OV-GM is less effective in generating systemic antitumor immunity compared with Heat-iOV-GM in murine tumor models. Similar to Heat-iOV-GM, the antitumor effects of live OV-GM also require Batf3-dependent CD103+ dendritic cells (DCs). Our results suggest that tumor lysis induced by the replication of oncolytic DNA viruses has a limited effect on the generation of antitumor immunity. On the contrary, the activation of Batf3-dependent CD103+ DCs and the alteration of the tumor immunosuppressive microenvironment is crucial for viral-based cancer immunotherapy.

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