Oncolytic viral therapy by bladder instillation using an E1A, E1B double-restricted adenovirus in an orthotopic bladder cancer model - 20/08/11
, Makoto Satoh a, Hisashi Abe b, Makoto Sunamura b, Takuya Moriya c, Shigeto Ishidoya a, Seiichi Saito a, Hirofumi Hamada d, Yoichi Arai a
Reprint requests: Hua Wang, M.D., Division of Urology, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, JapanAbstract |
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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Vol 68 - N° 3
P. 674-681 - septembre 2006 Retour au numéro
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