Attenuated Multimutated Herpes Simplex Virus-1 Effectively Treats Prostate Carcinomas With Neural Invasion While Preserving Nerve Function

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Infectious Diseases / Bacteria / Viruses;  Men's health
Article Date: 23 Mar 2008 - 0:00 PDT

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UroToday.com - In the online version of the FASEB Journal, Dr. Kelly and associates from Memorial Sloan-Kettering Cancer Center report that oncolytic therapy using HSV engineered to minimize neurotoxicity holds clinical promise. Herpes oncolytic vectors are effective gene transfer agents with attenuated toxicity to normal cells. These are replication competent viruses that have potent antitumor activity by inducing direct tumor cell lysis.

The researchers genetically engineered oncolytic herpes vectors from HSV type-1 (NV1023), a wild-type strain and tested it in vitro and in vivo. LNCaP and DU145 cells died in culture by day 3-5, but PC3 cells were more resistant. As a positive control, wild-type HSV-1 in vivo injection caused systemic disease, total paralysis and 22% weight loss by day 5. In contrast, the NV1023 treated mice survived up to >60 days, when the study was concluded. No significant toxicity attributable to the virus such as change in nerve function, body weight, behavior, skin condition, infections or mortality was observed. Histologic analysis of the nerves performed 7 days after inoculation with NV1023 demonstrated only Wallerian degeneration.

In vivo, the left sciatic nerve was exposed and PC3 and DU145 CaP cells injected. The establishment of infiltrating tumors was confirmed with a stereoscope at day 7, and then injected with NV1023 or saline. At day 7, all mice had established tumors and in the saline treated group all mice had onset of paralysis at week 4 with complete paralysis by week 8. Mice treated with a single intraneural injection of NV1023 had normal nerve function and significant inhibition of tumor size and inhibition of neural invasion. All control mice had significant proximal nerve invasion, but all the NV1023 mice had no evidence of proximal nerve invasion.

These data demonstrate that NV1023 is safe in immunosuppressed mice, and may offer a treatment approach to prostate cancer and other neurotrophic tumors.

Kelly K, Brader P, Rein A, Shah JP, Wong RJ, Fong Y, Gil Z

FASEB J. 2008 Jan 30
doi: 10.1096/fj.07-097808

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS Professor & Chairman Department of Urology University of California, Davis, School of Medicine Sacramento, CA

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