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Pexastimogene devacirepvec (Pexa-Vec) is an oncolytic immunotherapy based on a modified Wyeth strain of the vaccinia virus. It is engineered for tumor selectivity through the deletion of the viral thymidine kinase (TK) gene, which restricts viral replication to proliferating cancer cells with high cellular TK levels. Additionally, the virus is engineered to express the human granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene to stimulate a systemic anti-tumor immune response. Pexa-Vec exerts its therapeutic effect through three primary mechanisms: direct oncolysis (viral replication leading to cell bursting), induction of active anti-tumor immunity, and disruption of tumor vasculature. While it was primarily developed for hepatocellular carcinoma (HCC), its development in that indication was significantly impacted by the termination of the Phase 3 PHOCUS trial. It continues to be investigated in various solid tumors, often in combination with immune checkpoint inhibitors like ipilimumab or cemiplimab.
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