Attenuated multimutated herpes simplex virus-1 effectively treats prostate carcinomas with neural invasion while preserving nerve function Journal Article

  

Authors:	Kelly, K.; Brader, P.; Rein, A.; Shah, J. P.; Wong, R. J.; Fong, Y.; Gil, Z.
Article Title:	Attenuated multimutated herpes simplex virus-1 effectively treats prostate carcinomas with neural invasion while preserving nerve function
Abstract:	Many cancers can cause disability and pain by invading nerves. In particular, prostate carcinoma 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 deteriorated quality of life. Therefore, there is a need for novel modalities that will selectively target cancer cells while preserving neural function. Herpes simplex viruses (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 establishment 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 carcinomas with NI in an in vivo murine model while preserving neural function. These findings may hold significant clinical implications for patients with prostate cancer or other neurotrophic tumors. © FASEB.
Keywords:	controlled study; mutation; dose response; drug efficacy; drug safety; nonhuman; drug megadose; neurotoxicity; animal cell; mouse; animals; mice; animal tissue; mus; low drug dose; tumor volume; animal experiment; animal model; cytotoxicity; drug effect; animalia; mus musculus; prostate cancer; prostatic neoplasms; mice, nude; immunocytochemistry; tumor burden; gene therapy; oncolytic herpes virus; murinae; simplexvirus; oncolytic virotherapy; neoplasms, experimental; herpesvirus 1, human; rats; neoplasm invasiveness; disease models, animal; nerve function; erectile dysfunction; herpes simplex virus 1; sodium chloride; perineural invasion; prostate carcinoma; oncolytic therapy; virus attenuation; virus mutation; sciatic nerve; nervous system neoplasms; human herpesvirus 1; herpes simplex virus nv1023; vaccines, attenuated
Journal Title:	FASEB Journal
Volume:	22
Issue:	6
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Date Published:	2008-06-01
Start Page:	1839
End Page:	1848
Language:	English
DOI:	10.1096/fj.07-097808
PUBMED:	18234972
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-44949157886&partnerID=40&md5=b5937a92b76e66787311e2e8d6a7ea8a
Notes:	--- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "CODEN: FAJOE" - "Source: Scopus"

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