TY - JOUR
T1 - Oncolytic viral therapy by bladder instillation using an E1A, E1B double-restricted adenovirus in an orthotopic bladder cancer model
AU - Wang, Hua
AU - Satoh, Makoto
AU - Abe, Hisashi
AU - Sunamura, Makoto
AU - Moriya, Takuya
AU - Ishidoya, Shigeto
AU - Saito, Seiichi
AU - Hamada, Hirofumi
AU - Arai, Yoichi
PY - 2006/9
Y1 - 2006/9
N2 - Objectives: To investigate the therapeutic effect of AxdAdB-3, a double-restricted oncolytic adenovirus harboring a mutant E1A and an E1B-55KD deletion, on human bladder cancer cell lines and the SCID mouse model of orthotopic bladder cancer. Methods: The cytopathic effects of AxdAdB-3 were evaluated in several cell lines (YTS-1, YTS-3, T24, J82, 5637) derived from human bladder or ureteral cancer and in a normal bladder mucosa-derived cell line (HCV29) with AxCAlacZ (control) or AxE1AdB (E1B-55KD-defective adenovirus) or dl922-947 (E1A-mutated adenovirus). The efficacy of bladder instillation therapy with AxdAdB-3 for orthotopic bladder cancer of SCID mice was investigated. The oncolytic effects were monitored by ultrasound examination. Results: AxdAdB-3 caused the oncolysis of bladder cancer cell lines in vitro, and it was more cytopathic than AxE1AdB or dl922-947 in the cancer cell lines. AxdAdB-3 was not cytotoxic against HCV29. Direct instillation of AxdAdB-3 into the bladder of the orthotopic model inhibited tumor growth, leading to significantly prolonged survival. Conclusions: Oncolytic viral therapy delivered by instillation of AxdAdB-3 is a promising tool for treating bladder cancer.
AB - Objectives: To investigate the therapeutic effect of AxdAdB-3, a double-restricted oncolytic adenovirus harboring a mutant E1A and an E1B-55KD deletion, on human bladder cancer cell lines and the SCID mouse model of orthotopic bladder cancer. Methods: The cytopathic effects of AxdAdB-3 were evaluated in several cell lines (YTS-1, YTS-3, T24, J82, 5637) derived from human bladder or ureteral cancer and in a normal bladder mucosa-derived cell line (HCV29) with AxCAlacZ (control) or AxE1AdB (E1B-55KD-defective adenovirus) or dl922-947 (E1A-mutated adenovirus). The efficacy of bladder instillation therapy with AxdAdB-3 for orthotopic bladder cancer of SCID mice was investigated. The oncolytic effects were monitored by ultrasound examination. Results: AxdAdB-3 caused the oncolysis of bladder cancer cell lines in vitro, and it was more cytopathic than AxE1AdB or dl922-947 in the cancer cell lines. AxdAdB-3 was not cytotoxic against HCV29. Direct instillation of AxdAdB-3 into the bladder of the orthotopic model inhibited tumor growth, leading to significantly prolonged survival. Conclusions: Oncolytic viral therapy delivered by instillation of AxdAdB-3 is a promising tool for treating bladder cancer.
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U2 - 10.1016/j.urology.2006.04.021
DO - 10.1016/j.urology.2006.04.021
M3 - Article
C2 - 16979729
AN - SCOPUS:33748942284
VL - 68
SP - 674
EP - 681
JO - Urology
JF - Urology
SN - 0090-4295
IS - 3
ER -