HSV1-thymidine kinase vector

HSV1-thymidine kinase (HSV-tk) vector therapy is a prominent example of gene-directed enzyme prodrug therapy (GDEPT), frequently referred to as suicide gene therapy. The approach involves using a viral vector—most commonly an adenovirus or retrovirus—to deliver the Herpes Simplex Virus Type 1 thymidine kinase gene into target cells, typically malignant tumors. Once the HSV-tk gene is expressed within the target cells, the resulting enzyme can phosphorylate nucleoside analogs such as ganciclovir (GCV) or acyclovir, which are administered systemically as prodrugs. The HSV-tk enzyme converts these prodrugs into monophosphate forms, which are subsequently converted by endogenous cellular kinases into toxic triphosphate metabolites. These metabolites act as potent DNA polymerase inhibitors and chain terminators, inducing apoptosis in the transduced cells. A critical feature of this system is the bystander effect, where the toxic metabolites spread to neighboring non-transduced tumor cells via gap junctions, enhancing the overall anti-tumor efficacy. This platform has been extensively evaluated in clinical trials for high-grade gliomas and localized prostate cancer.

Brand names

CereproProstAtak

Other names

HSV-tk gene therapyHerpes simplex virus thymidine kinase vectorHSV-tk/GCV systemSuicide gene therapyGDEPT