Oncolytic Virotherapy for Prostate Cancer by E1A, E1B Mutant Adenovirus

Objectives: To report our therapeutic results in prostate cancer using double-mutated adenovirus AxdAdB-3, which has a mutation of E1A and deletion of E1B 55KD. Advanced prostate cancer can harbor multiple genetic alterations, including p53 and Rb/E2F/p16, and is often refractory to hormonal ablation. Virotherapy has been used to target these genetic abnormalities using mutant oncolytic adenovirus for the management of other cancers. Methods: The cytopathic effects of AxdAdB-3 were examined in human prostate carcinoma cell lines (DU145, PC3, and LNCaP) and human normal prostate-derived cell lines (PrEC and PrSC) with AxE1AdB and dl922-947 by crystal violet staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The therapeutic efficacy of AxdAdB-3 for the treatment of prostate cancer was investigated in an orthotopic prostate cancer model established with DU145 in severe combined immunodeficiency (SCID) mice. Results: AxdAdB-3 induced potent cytopathic effects in the prostate cancer cell lines tested. AxdAdB-3 showed no cytotoxicity in the normal prostate-derived cell lines PrEC and PrSC. In vivo, AxdAdB-3 showed apparent antitumor effect in the orthotopic prostate cancer model and significantly improved survival. Conclusions: These results suggest that AxdAdB-3 could be a promising tool for virotherapy against prostate cancer in patients with disease resistant to hormonal therapy.