An HSV-1 amplicon system for prostate-specific expression of ICP4 to complement oncolytic viral replication for in vitro and in vivo treatment of prostate cancer cells.
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| Abstract |
The aim of the present study was to determine whether a prostate-specific amplicon, containing a probasin-derived promoter (ARR(2)PB) upstream of an essential Herpes simplex virus-1 (HSV-1) viral gene, infected-cell polypeptide 4 (ICP4), could complement an HSV-1 helper virus with this gene deleted (ICP4-) and cause lytic replication specifically in prostate cancer cells. Two amplicon constructs, CMV-ICP4 and ARR(2)PB-ICP4, were packaged by a replication-deficient ICP4- helper virus. The amplicon viruses could complement ICP4- helper viruses to efficiently replicate and cause cell lysis in prostate cancer cells. Intratumoral injection of LNCaP human prostate cancer xenografts with either amplicon/helper virus resulted in >75% reduction in tumor volume and serum prostate specific antigen (PSA). Histological and Q-PCR (quantitative PCR) analyses indicated that the toxicity in nontumor tissues was much lower with ARR(2)PB-ICP4 than with CMV-ICP4 amplicon/helper virus. In conclusion, a replication-deficient HSV-1 virus could be complemented by an amplicon virus to restore its oncolytic activity in a tissue-specific and low toxicity fashion, illustrating that this approach could be a potentially useful strategy for developing an oncolytic viral therapy for prostate cancer.
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| Authors | C Y-F Lee, L X Bu, P S Rennie, W W-G Jia |
| Journal | Cancer gene therapy (Cancer Gene Ther) Vol. 14 Issue 7 Pg. 652-60 (Jul 2007) ISSN: 0929-1903 [Print] England |
| PMID | 17479106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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