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AdV-HSV1-TK + AdV-Flt3L + valacyclovir is an investigational combination gene therapy developed by the University of Michigan Rogel Cancer Center for the treatment of recurrent malignant brain tumors, including diffuse hemispheric glioma and diffuse midline glioma. The therapy utilizes two adenoviral vectors: AdV-HSV1-TK, which expresses the herpes simplex virus type 1 thymidine kinase (HSV1-TK) enzyme, and AdV-Flt3L, which expresses the Fms-like tyrosine kinase 3 ligand (Flt3L). The vectors are injected into the tumor resection cavity. HSV1-TK converts the co-administered oral prodrug valacyclovir into a cytotoxic metabolite that selectively kills actively dividing tumor cells. Simultaneously, Flt3L recruits and activates dendritic cells to the brain, stimulating a systemic anti-tumor immune response. This dual approach aims to provide both immediate tumor cell death and long-term immune surveillance.
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