PexaVec

PexaVec, also known as JX-594, is a genetically engineered oncolytic vaccinia virus developed for cancer therapy by Jennerex, later acquired by SillaJen. The virus carries a transgene for granulocyte-macrophage colony-stimulating factor (GM-CSF) and has deletions in the viral thymidine kinase gene and vaccinia growth factor, which are intended to limit replication in normal tissues and drive tumor-selective activity.

The mechanism of action combines direct oncolysis with an anti-tumor immune response. PexaVec is designed to preferentially replicate in cancer cells, causing lysis and release of tumor antigens, while the expressed GM-CSF aims to recruit dendritic cells and other immune effectors to stimulate systemic anti-tumor immunity. This approach seeks to convert injected or disseminated tumors into vaccines that prime lasting immune responses against cancer cells.

In clinical development, PexaVec has been evaluated in hepatocellular carcinoma and other solid tumors, with trials employing intratumoral injections and/or intravenous administration. Reported outcomes have included occurrences of tumor responses and disease stabilization in some patients, alongside a generally manageable safety profile. Common adverse events include flu-like symptoms and local injection-site reactions, with severe events being less frequent.

Regulatory status and trial outcomes have tempered enthusiasm. A Phase III trial in hepatocellular carcinoma evaluated overall survival but did not demonstrate a statistically significant benefit, and development in that indication has faced challenges. As of now, PexaVec has not received regulatory approval. Research continues into optimization and combination strategies with other cancer therapies, such as immune checkpoint inhibitors, but no approved indications exist.