Mutant herpes simplex virus type 1 thymidine kinase (HSV-1 TK) encoded by OTS-412 (HSV-1 TK (mutant))

The mutant herpes simplex virus type 1 thymidine kinase (HSV-1 TK) encoded by OTS-412 is an engineered suicide gene product utilized within an oncolytic vaccinia virus (OVV) platform [1, 3]. Developed by Bionoxx, this specific mutant is a truncated version of the HSV-1 TK enzyme (approximately 36.1 kDa) resulting from a point mutation (c. 991 C>T) [3, 8]. Its primary biological function is to serve as a safety switch and a therapeutic engine by phosphorylating nucleoside analogs such as ganciclovir (GCV) [1, 7]. While wild-type HSV-1 TK can sometimes interfere with the tumor-selective replication of vaccinia viruses, the OTS-412 mutant maintains high tumor selectivity while remaining highly sensitive to GCV-mediated inhibition [1, 8]. In a clinical context, the enzyme acts as a suicide protein; it converts the relatively non-toxic prodrug ganciclovir into ganciclovir triphosphate, which incorporates into the DNA of infected cancer cells, leading to chain termination and apoptosis [1, 11]. This mechanism not only kills the tumor cells directly but also provides a pharmacological means to halt viral replication if safety concerns arise [4, 7]. OTS-412 is currently being evaluated in Phase 1 clinical trials for patients with treatment-refractory solid tumors, often in combination with hydroxyurea or immune checkpoint inhibitors like atezolizumab to maximize anti-tumor efficacy [4, 6].

Other names

Truncated herpes simplex virus type 1 thymidine kinaseOTS-412 transgene productMutant HSV-tkHSV-1 TK (mutant)

Suicide gene therapy involving the enzymatic conversion of the prodrug ganciclovir into a cytotoxic triphosphate metabolite that inhibits DNA synthesis and induces apoptosis.