Herpes oncolytic vectors effectively treat prostate carcinomas with neural invasion while preserving nerve function

Abstract

Prostate carcinoma has a high propensity for neural invasion (NI) and resection of these tumors often leads to erectile dysfunction. We hypothesized that oncolytic therapy using attenuated herpes simplex virus (HSV) will selectively target cancer cells invading nerves while preserving neural function.Prostate cancer cell lines PC3, DU145, and LNCap were infected with HSVs (NV1023 and NV1066) in vitro and cytotoxicity was assessed over 7 days. HSV had significant oncolytic effect on all prostate cancer cell lines. An in vivo model of NI was established by implanting prostate carcinoma cells in the sciatic nerves of nude mice. Mice were treated with NV1023 or saline 7 days after establishment of tumors. Treatment with attenuated viruses had no toxic effect on nerves (n=30). Significant reduction in tumor size and inhibition of NI was found 6–8 weeks after treatment (P <0.005, n=30). The control animals developed complete paralysis <5 weeks post‐treatment, whereas most NV1023‐treated animals had preserved nerve function >12 weeks after treatment (P <0.0001, n=7–10).Attenuated HSVs effectively treat prostate carcinomas with NI, while preserving nerve function. These findings may hold significant clinical implications for prostate cancer patients and for other neurotrophic tumors.Research support was provided by FAMRI.