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**stimotimagene copolymerplasmid + ganciclovir** is a combination cancer gene therapy based on direct intratumoral administration of a supercoiled plasmid DNA (stimotimagene copolymerplasmid) that encodes the herpes simplex virus thymidine kinase (HSV1-tk) gene, followed by systemic administration of the antiviral agent ganciclovir. Inside tumor cells, the plasmid is taken up and expresses the HSV1-tk enzyme, which phosphorylates ganciclovir to its triphosphate form. Ganciclovir triphosphate is then incorporated into DNA during replication, leading to chain termination and apoptosis. This system acts as a "suicide gene therapy"—only transfected tumor cells expressing HSV1-tk convert ganciclovir into its cytotoxic form, achieving selective intratumoral cytotoxicity. The combination is being developed primarily for solid tumors, with current Phase 1 trials for advanced malignant solid neoplasms, anus neoplasms, breast cancer, and melanoma[1][5][7]. Gene Surgery is reported as the developer and trial sponsor for stimotimagene copolymerplasmid. Ganciclovir is a synthetic nucleoside analog, FDA-approved for other indications such as cytomegalovirus infection, but here used as part of a targeted gene therapy regimen[6][4].
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