Herpes simplex virus type 1 mutant HF10 oncolytic viral therapy for bladder cancer

Abstract

Objectives To investigate the antitumor effects of the oncolytic herpes simplex virus (HSV) type 1 mutant HF10 on human and murine bladder cancer cells (T24 and MBT-2) in vitro and in immunocompetent mouse models. Methods In vitro viral oncolytic activity and the replication ability of HF10 were measured in T24 and MBT-2 cells. To evaluate the therapeutic efficacy of HF10, disseminated peritoneal and bladder cancer models using MBT-2 cells were established in C3H/HeJ mice. The therapeutic efficacy was estimated from the survival rates and histopathologic analyses. Results HF10 replicated well in both T24 and MBT-2 cells, and it induced extensive cell lysis. Treatment with HF10 significantly prolonged the survival periods and increased the survival rates in both models tested. Immunohistochemical studies showed that HSV antigens were detected in the bladders 1 and 3 days after intravesical treatment with HF10 in nonimmunized mice, but only at 1 day after HF10 treatment in preimmunized, HSV-1 antibody-positive mice. A large number of inflammatory cells infiltrated into the bladder mucosa at 3 days after HF10 treatment in the preimmunized mice. Conclusions These results suggest that HF10, a novel oncolytic HSV-1 mutant, is a promising agent for the treatment of superficial bladder cancer.