Herpes simplex virus enhanced thymidine kinase (HSV-eTK)

Herpes simplex virus enhanced thymidine kinase (HSV-eTK) is a genetically engineered variant of the viral thymidine kinase enzyme, optimized for superior catalytic efficiency in activating nucleoside analog prodrugs. In the GEN2 therapeutic platform developed by GenVivo, the gene encoding HSV-eTK is delivered to tumor cells via a non-replicating vector, where it is expressed alongside the immunostimulatory cytokine GM-CSF [4, 6]. The primary function of HSV-eTK is to selectively phosphorylate prodrugs such as valganciclovir into toxic metabolites that inhibit DNA polymerase and cause lethal DNA chain termination [4, 15]. This targeted suicide gene approach induces apoptosis specifically in transduced cancer cells, leading to the release of a broad spectrum of patient-specific tumor neoantigens [1, 8]. The simultaneous local production of GM-CSF recruits and activates dendritic cells and other immune effectors, facilitating the presentation of these neoantigens to the systemic immune system [4, 10]. Consequently, the therapy aims to elicit a robust, durable, and systemic anti-tumor immune response capable of targeting both the primary tumor and distant metastases [1, 6].

Other names

HSV-tk-m2Mutated herpes simplex virus thymidine kinaseOptimized viral thymidine kinaseHSV-eTKSuicide gene product

HSV-eTK catalyzes the phosphorylation of nucleoside analogs (prodrugs) such as ganciclovir into monophosphate forms. Host cellular kinases then convert these into triphosphate metabolites, which act as competitive inhibitors of deoxyguanosine triphosphate (dGTP) and cause DNA chain termination during replication, leading to tumor cell apoptosis [4, 14, 15].