Oncolytic viral therapy by bladder instillation using an E1A, E1B double-restricted adenovirus in an orthotopic bladder cancer model.

Abstract

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.

• Authors: Hua Wang, Makoto Satoh, Hisashi Abe, Makoto Sunamura, Takuya Moriya, Shigeto Ishidoya, Seiichi Saito, Hirofumi Hamada, Yoichi Arai
• Journal: Urology (Urology) Vol. 68 Issue 3 Pg. 674-81 (Sep 2006) ISSN: 1527-9995 [Electronic] United States
• PMID: 16979729 (Publication Type: Journal Article)

Topics

• Adenoviridae (genetics)
• Administration, Intravesical
• Animals
• Cell Line, Tumor
• Disease Models, Animal
• Humans
• Mice
• Mice, SCID
• Oncolytic Virotherapy (methods)
• Urinary Bladder Neoplasms (drug therapy)