ganciclovir + sitimagene ceradenovec

Ganciclovir + sitimagene ceradenovec is a combination therapy used in the context of gene-directed enzyme prodrug therapy (suicide gene therapy) for high-grade glioma. Sitimagene ceradenovec is an adenoviral vector encoding the herpes simplex virus thymidine kinase (HSV-TK) gene, which is delivered directly into tumor tissue after surgical resection. Once inside tumor cells, the HSV-TK gene is expressed, making these cells susceptible to ganciclovir, an antiviral prodrug. When administered systemically, ganciclovir is phosphorylated by HSV-TK into a toxic nucleotide analog that induces DNA chain termination and cell death specifically in transduced tumor cells. This approach also leverages a "bystander effect," where neighboring non-transduced tumor cells are killed due to diffusion of toxic metabolites or immune-mediated mechanisms. The combination has been studied primarily for operable high-grade glioma and has shown increased time to death or re-intervention compared with standard care in clinical trials[1][2][6][9].