Targeting Prostate Cancer for Gene Therapy Utilizing Lentivirus and Oncolytic VSV Virus
Abstract
Prostate cancer is the most commonly diagnosed non-skin carcinoma, and one of the leading causes of cancerrelated deaths in North American men. Presently there are no curative therapies available for advanced metastatic prostate cancer. Oncolytic viral therapy provides an opportunity to efficiently kill primary and metastatic cancer cells while sparing normal cells. Vesicular Stomatitis Virus (VSV) is an oncolytic virus which is able to replicate in cells with a defective interferon (INF) response. Here, we examined the effect of a mutated VSV (AV3), which expresses luciferase and has an enhanced INF-sensitivity, on the viability of prostate tumours that develop in prostate-specific PTEN null transgenic mice. Prostates of PTEN knockout and control mice were injected with 5x108 pfu/ml of VSV(AV3) and monitored for luminescence over a 96h time period using the IVIS-Xenogen machine to track the virus distribution. Plaque analyses for live virus n tissues extracted at various time points revealed that VSV(AV3)predominantly replicated in the prostates of transgenic PTEN knockout mice. Additionally, using TUNNEL staining of paraffin embedded tissues, we demonstrated that VSV(AV3) is capable of selectively infecting and killing malignant prostate cells while sparing normal cells. This cancer-specific cell death was not due to infiltration of neutrophils into the prostate tumours of PTEN null mice's has been reported for other tumour mode. However, there was an increase in macrophage and Blymphocyte infiltration into the prostates of PTEN null mice compared to control mice. In conclusion, VSV(AV3) is able to replicate and selectively kill the prostate cancer cells that develop in the PTEN null mouse and hence prove clinically useful for treating locally advanced prostate cancer while sparing normal prostate tissue.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA506438
Entities
People
- Maryam Moussavi
Organizations
- University of British Columbia