Gene therapy for bladder cancer using adenoviral vector

Background and Purpose: Bladder cancer is common. Current treatment for pat ients with superficial bladder cancer involves transurethral resection foll owed by adjuvant bacillus Calmette-Guerin (BCG) administration. Adjuvant BC G has been reported to be effective in 38% to 68% of patients; however, mor e than 30% of patients do not respond. Because p53 mutations are common amo ng superficial bladder cancers, we tested the feasibility of using p53 as a gene therapy agent for targeting superficial tumors, which are easily acce ssible using an intravesical approach. Materials and Methods: Wild-type p53 was transduced into various human and murine bladder cancer cell lines (HTB9, KU-1, and MBT-2) using a recombinan t adenoviral vector (Ad5CMV-p53) in vitro, Also, subcutaneous tumors were e stablished and then treated with intratumoral injection of Ad5CMV-p53 or co ntrol viruses. Results: In vitro assays revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV- PA vector or untreated control cells. In vivo studies using subcutaneous bl adder tumor models established in syngeneic mice demonstrated that the rate of tumor growth and volume was reduced to a greater extent by 14 days of i ntratumoral injection of Ad5CMV-p53 rather than Ad5CMV-PA, Furthermore, the survival of host animals bearing tumors that were infected with Ad5CMV-p53 was significantly longer than that of the control group treated with Ad5CM V-PA (P < 0.01). Conclusion: Our data suggest that Ad5CMV-p53 is effective in suppressing bl adder cancer growth and improving host survival.