【摘 要】
：
The aim of the present study was to determine whether herpes simplex virus-1 (HSV-1) can be made prostate-specific and oncolytic by either co-infecting an amplicon containing a probasin-derived promot
【机 构】
：
Brain Research Center University of British Columbia Canada
【出 处】
：
BIT Life Sciences 1st Annual World Cancer Congess-2008(2008中
论文部分内容阅读
The aim of the present study was to determine whether herpes simplex virus-1 (HSV-1) can be made prostate-specific and oncolytic by either co-infecting an amplicon containing a probasin-derived promoter (ARR2PB) upstream of an essential HSV-1 gene icp4 to complement a HSV-1 helper virus with this gene deleted (icp4-) or by creating a recombinant virus with the ARR2PB promoter replacing the promoter of another essential HSV-1 gene icp27 (ARR2PB27).Two amplicon constructs, CMV-ICP4 and ARR2PB-ICP4,were packaged by a replication-deficient icp4-helper virus.While amplicon CMV-ICP4 complemented icp4-helper viruses to replicate in Vero cells, the ARR2PB-ICP4 was more specific for prostate cancer cells, causing virus replication and cell lysis in an androgen dependent fashion.Intra-tumoral injection of LNCaP human prostate cancer xenografts with either amplicon plus helper virus resulted in >75% reduction in tumor volume and serum PSA.Histological and Q-PCR analyses indicated that toxicity in non-tumor tissues was much lower with ARR2PB-ICP4 than with CMV-ICP4 amplicon/helper virus.
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