Systemic Oncolytic Cytokine HSV Therapy of Prostate Cancer
Abstract
The purpose of the present work is to evaluate the use of oncolytic HSV vectors (oHSV) and their cytokine-containing derivatives as potential therapeutic modalities in the transgenic TRAMP mouse, which recapitulates the developmental hallmarks in treating prostate cancer. We show that expression of interleukin 12 (IL-12) from NV1042 virus, a derivative of NV1023, was substantially effective at reducing the frequency of developing prostate cancer and lung metastases, even when the mice were treated after the onset of metastasis at 18 weeks of age. In October of 2007, we published this work in Cancer Research. Furthermore, we have extended these finding by using a novel complementary approach. Human prostate cancer tissues derived from radical prostatectomies were used in a organotypic culture system to further assess the efficacy of oncolytic HSV virotherapy. Our data shows that while G47 delta specifically targets epithelial cells but not the surrounding stroma, wild-type HSV is promiscuous in that it also infects prostate stroma. Lastly, G47 delta was shown to be more at least 10-fold more effective than G207, from which G47 delta was made, in its ability to replicate in these cancer specimens.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2008
- Accession Number
- ADA492787
Entities
People
- Brent J. Passer
Organizations
- Massachusetts General Hospital