Ad.RSVtk

Ad.RSVtk is a replication-deficient adenoviral vector (typically E1-deleted or E1/E4-deleted) designed for suicide gene therapy in various localized malignancies. It carries the herpes simplex virus type 1 thymidine kinase (HSVtk) gene under the transcriptional control of the Rous sarcoma virus (RSV) promoter. The therapeutic strategy involves the administration of the vector into the tumor site, followed by systemic treatment with the antiviral prodrug ganciclovir (GCV). The HSVtk enzyme expressed by the transduced cells phosphorylates ganciclovir into ganciclovir monophosphate, which is then converted by endogenous cellular kinases into ganciclovir triphosphate. This active metabolite acts as a deoxyguanosine triphosphate analogue, inhibiting DNA polymerase and causing premature DNA chain termination, leading to cell death. A key feature of this system is the "bystander effect," where the toxic metabolites spread to adjacent non-transduced cells via gap junctions, enhancing the overall anti-tumor efficacy. Ad.RSVtk has been evaluated in Phase I clinical trials for malignant pleural mesothelioma and has shown preclinical activity in head and neck, ovarian, and lung cancers.

Other names

Ad.RSV-tkadenoviral-mediated herpes simplex virus thymidine kinase gene therapy