Genetic Radiotherapy of Prostate Cancer
Final rept., 1 Dec 2001-30 Nov 2004
ALABAMA UNIV IN BIRMINGHAM
Pagination or Media Count:
The goal to achieve a high intra-tumoral concentration of 5-fluoro-uracil 5-FU via molecular chemotherapy employing adenoviral Ad vectors encoding the genes for somatostatin receptor subtype 2SSTr2 and cytosine deaminase CD which converts the prodrug 5-fluoro-cytosine 5-FC to 5-FU under control of the cyclo-oxygenase-2 Cox-2 tumor-specific promoter was achieved. We evaluated novel two-gene Ad vectors 1 a native fiber Ad AdCMVCDCMVSSTr2 and 2 Ad under control of the Cox-2 promoter expressing CD and SSTr2. The vectors were tested for SSTr2 and CD expression employing membrane receptor binding in vitro with 125somatostatin and 99mTc-P2045 that binds to SSTr2, conversion of 5-FC to 5-FU, and cytotoxicity against Ad infected cells in the presence of 5-FC. The vectors were evaluated in vivo for SSTr2 expression and CD expression. Efforts to produce RGD modified vectors expressing CD and SSTr2 under control of the Cox-2L promoter were not successful. We identified chimeric Ad53 virus with the Cox-2L promoter driving CD and SSTr2 to have therapeutic efficacy against prostate cancer xenografts, and identified that Ad virus expressing CDUPRT was more efficacious than CD in combination with 5-FC and radiation therapy.
- Medicine and Medical Research