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**GEN2** is an investigational, replication-incompetent gene-transfer vector developed by GenVivo for cancer immunotherapy. The vector carries genes encoding enhanced herpes simplex virus thymidine kinase and human granulocyte-macrophage colony-stimulating factor. Following transduction of tumor cells, sequential administration of the oral prodrug valganciclovir enables HSV-eTK-mediated formation of a cytotoxic ganciclovir metabolite, causing DNA chain termination in proliferating tumor cells and releasing tumor antigens, including neoantigens. Locally expressed GM-CSF is intended to enhance antigen presentation and antitumor immune activation. GEN2 is an off-the-shelf therapy that does not require individualized tumor sequencing or biopsy-based neoantigen selection. It has been evaluated in Phase 1 studies in hepatocellular carcinoma, liver-metastatic solid tumors, and other advanced solid tumors.
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