Integrating Molecular Imaging Approaches to Monitor Prostate Targeted Suicide and Anti-angiogenic Gene Therapy

摘要

To develop safe and efficient gene therapy protocol for advanced stages of prostate cancer, we aimed to combine the selective suicide and anti- angiogenic gene therapy approaches into an effective targeted treatment for prostate cancer. We propose to incorporate a strong and tissue-specific two- step transcriptional amplification(TSTA) system to mediate prostate-targeted thymidine kinase (sr39tk) gene expression in prostate cancer cells. This targeted vector can be also utilized as a positron emission tomography (PET) reporter. We have shown that the TSTA-sr39tk adenoviral vector, in combination with prodrug ganciclovir, efficiently killed tumor cells whereas it exhibited minimal liver toxicity compared to CMV-sr39tk vector in human prostate tumor xenografed mice model. In addition, the anti-angiogenic adenoviral vectors expressing TSP1 and ADAMTS1 exhibited a strong inhibitory effect on the initial development of hormone refractory prostate cancer CWR22Rv1 cell lines in nudemice. We foresee that anti-angiogenic adenoviral vectors, in combination with the prostate targeted TSTAvector, will be an excellent therapeutic option for advanced stages of prostate cancer.