Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence

It is estimated that there will be > 184,500 new cases of prostate cancer a nd 42,000 prostate cancer deaths in the United States this year. In the maj ority of patients diagnosed with prostate cancer, the disease will be too a dvanced for cure with standard medical treatment. New therapeutic strategie s against advanced prostate cancer are desperately needed. As alterations i n tumor-suppressor gene p16 are common in prostate cancer, one novel approa ch is gene therapy using a replication-deficient, E1/E3-deleted adenovirus type 5 containing a p16 under the control of a truncated Rous sarcoma virus promoter (AdRSVp16). In vitro, PC-3 cells that had been stably transfected with p16 expression vector under the control of an inducible promoter had a 70% reduction in cell number compared with the parental and control vecto r-transfected PC-3 cells. Similarly, AdRSVp16 significantly inhibited the g rowth of PPC-1 and PC-3 prostate cancer cells in culture. Furthermore, PPC- 1 tumors grown in nude mice treated by a single injection of AdRSVp16 had a marked reduction in tumor size compared with untreated control-treated or viral control-treated PPC-I tumors. Animals bearing tumors treated with AdR SVp16 also had longer survival. Adenovirally mediated expression of transge ne was detected in xenograft tumors for at least 2 weeks. Taken together, t hese results suggest that AdRSVp16 should be considered for prostate cancer gene therapy in human clinical trials.