Herpes simplex virus thymidine kinase (HSV-tk) gene product

Class

Non-replicating adenoviral vector suicide gene therapy

Pathway

Intratumoral HSV-tk gene delivery converts prodrug valacyclovir into a cytotoxic nucleotide analogue that disrupts DNA replication, plus adenoviral-capsid-driven immune (T-cell) recruitment

Notes

original target text: Herpes simplex virus thymidine kinase (HSV-tk) gene product, sensitizing cells to valacyclovir

This mechanism uses a gene delivered by a non-replicating adenoviral vector to introduce a foreign enzyme, herpes simplex virus thymidine kinase (HSV-tk), into tumor cells. HSV-tk is not naturally present in human cells and has a broader substrate range than human kinases, allowing it to activate certain antiviral prodrugs, such as valacyclovir, that human enzymes would otherwise leave largely inert. Once activated inside a transduced cell, the prodrug is converted into a nucleotide analogue that interferes with DNA synthesis, killing the cell as it attempts to divide. Because tumor cells divide more frequently than most surrounding tissue, this selectively damages rapidly proliferating cancer cells while sparing quiescent normal cells. The approach, sometimes called suicide gene therapy, also uses the adenoviral vector's own proteins to draw immune attention to the injected tumor site, potentially recruiting T-cells against tumor antigens as cells die. This dual action—direct cytotoxicity plus local immune stimulation—broadly matters in solid tumors where achieving both durable local control and a systemic anti-tumor immune response is a persistent therapeutic goal. It represents a strategy for converting a tumor into a site of localized drug activation and immune priming, rather than relying on systemic chemotherapy exposure.