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Ad-hCMV-Flt3L + Ad-hCMV-TK is a combination gene therapy consisting of two replication-deficient adenoviral vectors. One vector encodes human Fms-like tyrosine kinase 3 ligand (Flt3L) under the control of the human cytomegalovirus (hCMV) promoter (Ad-hCMV-Flt3L), and the other encodes herpes simplex virus type 1 thymidine kinase (HSV1-TK) also under hCMV promoter control (Ad-hCMV-TK). This therapy is designed for local administration into the resection cavity following surgical removal of high-grade gliomas. HSV1-TK acts as a suicide gene; when patients receive valacyclovir, HSV1-TK phosphorylates it to toxic metabolites that selectively kill dividing tumor cells. Flt3L is a cytokine that recruits and differentiates dendritic cells within the tumor microenvironment, enhancing antigen presentation and stimulating anti-tumor immune responses. The combined approach aims to induce immunogenic cell death in residual tumor cells while simultaneously activating an adaptive immune response against glioma antigens[1][5][6]. Preclinical studies demonstrated efficacy in animal models, and phase I clinical trials have shown safety and feasibility in patients with high-grade glioma[2][4].
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