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Updated: Jul 20, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Oncolytic viral therapy by bladder instillation using an E1A, E1B double-restricted adenovirus in an orthotopic
Hua Wang1, Makoto Satoh, Hisashi Abe
1Division of Urology, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. wang@uro.med.tohoku.ac.jp
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.
Insights
Oncolytic adenovirus AxdAdB-3 effectively targets human bladder cancer cells and inhibits tumor growth in mice. This oncolytic viral therapy shows promise for treating bladder cancer.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Bladder cancer remains a significant health concern with limited therapeutic options.
- Oncolytic viruses offer a targeted approach to cancer treatment by selectively destroying cancer cells.
- Developing effective oncolytic adenoviruses requires careful genetic engineering for enhanced safety and efficacy.
Purpose of the Study:
- To evaluate the therapeutic potential of AxdAdB-3, a novel oncolytic adenovirus, against human bladder cancer.
- To assess the in vitro cytopathic effects of AxdAdB-3 on various human bladder cancer cell lines.
- To determine the in vivo efficacy of AxdAdB-3 in an orthotopic SCID mouse model of bladder cancer.
Main Methods:
- In vitro studies involved exposing human bladder cancer cell lines (YTS-1, YTS-3, T24, J82, 5637) and a normal cell line (HCV29) to AxdAdB-3, AxE1AdB, dl922-947, or AxCAlacZ.
- In vivo efficacy was assessed using an orthotopic bladder cancer model in SCID mice treated with AxdAdB-3 via bladder instillation.
- Oncolytic effects and tumor progression were monitored using ultrasound examinations.
Main Results:
- AxdAdB-3 demonstrated significant oncolysis of bladder cancer cell lines in vitro, exhibiting greater cytopathic effects than control adenoviruses.
- AxdAdB-3 showed no cytotoxicity against normal bladder mucosa cells (HCV29), indicating tumor selectivity.
- Bladder instillation of AxdAdB-3 in the SCID mouse model effectively inhibited tumor growth and significantly prolonged animal survival.
Conclusions:
- AxdAdB-3 is a potent oncolytic adenovirus with selective activity against human bladder cancer cells.
- Intravesical administration of AxdAdB-3 represents a promising therapeutic strategy for bladder cancer.
- Oncolytic viral therapy using AxdAdB-3 warrants further investigation for clinical application in bladder cancer treatment.
