Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer
Final rept. 1 Feb 2003-31 Jan 2007
CALIFORNIA UNIV LOS ANGELES
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Hormone refractory and metastatic prostate cancer are not well understood. Better animal models, diagnostic and treatment modalities are sorely needed for these advanced stages of disease. We have developed metastatic prostate cancer animal models that can be monitored by molecular imaging. To target metastatic disease, we have incorporated a highly potent and prostate-specific transcriptional regulatory system TSTA in adenoviral vectors such that the expression of imaging reporter gene and therapeutic gene is restricted to prostate cancer cells. Using the prostate-specific TSTA vectors, we were able to map the presence of lymph node metastases by optical or PET imaging. An extension of the TSTA technology is to regulate the expression of viral E1 replication control gene products such that the lytic viral replicative process is directed at prostate-specific tumor lysis. With extensive molecular engineering, we have demonstrated the feasibility and the functionality of the prostate-targeted oncolytic system. The immediate future plan is to apply the oncolytic viruses in an image guided oncolytic viral therapy to treat metastatic disease in pre-clinical models of prostate cancer.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology