AB087. The biotherapy for bladder cancer

Abstract: The high frequency of recurrence and poor survival rate of bladder cancer demand exploration of novel strategies. Biotherapy strategies include immunotherapy, gene therapy, inducing cell apoptosis, and so on. Precious studies indicated that BCG could effectively prevent tumor recurrence, and significantly reduce tumor progression. Our studies showed that BCG combined with epirubicin could more effectively inhibit tumor recurrence and progression. But BCG also has its own side effects. Studies showed that Wan Te Puan induce tumor cell apoptosis by inhibit EGFR signaling pathway, and induce the conversion of macrophage and dendritic cells activation through improving immune microenvironment. We demonstrated that modified DC by cytokines has better antitumor effect. Promisingly, our group constructed a bladder cancer-specific adenovirus carrying E1A-androgen receptor (AR) under the control of UPII promoter and prostate stem cell antigen enhancer (PSCAE), designated as Ad/PSCAE/UPII/E1A-AR, and investigated its antitumor effects in vitro and in vivo. We demonstrated that Ad/PSCAE/UPII/E1A-AR could be selectively replicated in bladder tumor cell lines (5637, BIU87, EJ and T24) when compared with control adenovirus Ad/PSCAE/UPII/Luc. In addition, we demonstrated that intratumoral injection of Ad/PSCAE/UPII/E1A-AR into established subcutaneous human EJ tumors in nude mice could significantly regress the growth of tumor and markedly prolong survival for tumor-bearing mice; on the other hand, saline-treated tumors continued to grow rapidly. Importantly, there is no evidence of cytotoxicity for normal human bladder cell line SVHUC-1 and hepatoma cell line SMMC7721. Our study also showed that radiotherapy and chemotherapy synergistically enhanced the antitumor effect of oncolytic adenovirus. We found that recombinant adenovirus Ad/PSCAE/UPII/E1A-AR appear safe with 5×10⁷ pfu and 5×10⁸ pfu intratumorally injection in mice, without any discernable effects on general health and behavior. Furthermore, our findings provide a promising therapeutic modality for the treatment of bladder cancer.

Keywords: Bladder cancer; biotherapy; BCG