Abstract
Immune checkpoint blockade (ICB) therapy has brought hope to many cancer patients, but the response rate is low in many cancer types, and acquired resistance to ICB can develop over time. Oncolytic viruses are promising therapeutic agents for advanced cancers. Modified vaccinia virus Ankara (MVA) is an attenuated, replication-deficient poxvirus safe for human use, making it a favorable platform for cancer immunotherapy. Our first-generation recombinant MVA has shown promising antitumor efficacy in multiple murine tumor models due to the deletion of the E5R gene (encoding an inhibitor of the DNA sensor cGAS) from the MVA genome and the insertion of two membrane-anchored transgenes – Flt3L and OX40L, which leads to the activation of the host innate and adaptive antitumor immunity.
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