Oncolytic viral therapy by bladder instillation using an E1A, E1B double-restricted adenovirus in an orthotopic bladder cancer model.
OBJECTIVE
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.
Wang
Hua
H
Division of Urology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. wang@uro.med.tohoku.ac.jp
Satoh
Makoto
M
Abe
Hisashi
H
Sunamura
Makoto
M
Moriya
Takuya
T
Ishidoya
Shigeto
S
Saito
Seiichi
S
Hamada
Hirofumi
H
Arai
Yoichi
Y
D000256:Adenoviridae / Q000235:genetics*; D000283:Administration, Intravesical; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D050130:Oncolytic Virotherapy / Q000379:methods*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*