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Attenuated multimutated herpes simplex virus‐1 effectively treats prostate carcinomas with neural invasion while preserving nerve function
Author(s) -
Kelly Kaitlyn,
Brader Peter,
Rein Avigail,
Shah Jatin P.,
Wong Richard J.,
Fong Yuman,
Gil Ziv
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-097808
Subject(s) - prostate cancer , medicine , oncolytic virus , du145 , lncap , in vivo , prostate , herpes simplex virus , cancer research , pathology , cancer , biology , immunology , virus , microbiology and biotechnology
Many cancers can cause disability and pain by invading nerves. In particular, prostate carci noma has a high propensity for neural invasion (NI) at an early stage. Attempted surgical treatment of tumors with NI often leads to erectile dysfunction and deteri orated quality of life. Therefore, there is a need for novel modalities that will selectively target cancer cells while preserving neural function. Herpes simplex vi ruses (HSVs) have a natural trophism for peripheral nerves. We hypothesized that oncolytic therapy using HSV engineered to minimize neurotoxicity would be appropriate for this clinical setting. Attenuated HSV (NV1023) injected to sciatic nerves of nude mice had no toxic effect on nerve function ( n =30). NV1023 had significant oncolytic effect on prostate carcinoma cells (PC3, DU145, and LNCap) in vitro. 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 establish ment of tumors. Significant reduction in tumor size and inhibition of NI was found 6–8 wk after treatment ( P <0.005). All animals treated with saline developed complete paralysis < 5 wk post‐treatment, whereas most NV1023‐treated animals had preserved nerve function >12 wk after treatment ( P <0.0001). We conclude that oncolytic therapy effectively treats prostate carci nomas with NI in an in vivo murine model while preserving neural function. These findings may hold significant clinical implications for patients with pros tate cancer or other neurotrophic tumors.— Kelly, K., Brader, P., Rein, A., Shah, J. P., Wong, R. J., Fong, Y., Gil, Z. Attenuated multimutated herpes simplex vi rus‐1 effectively treats prostate carcinomas with neural invasion while preserving nerve function. FASEB J. 22, 1839–1848 (2008)