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Updated: Jul 7, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Tumor-selective replication of an oncolytic adenovirus carrying oct-3/4 response elements in murine metastatic
Chao-Liang Wu1, Gia-Shing Shieh, Chao-Ching Chang
1Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan.
Purpose:
Oncolytic adenoviruses are attractive therapeutics for cancer because they selectively replicate in tumors. However, targeting tumor metastasis remains a major challenge for current virotherapy for cancer. Oct-3/4 is specifically expressed in embryonic stem cells and tumor cells. Oct-3/4 highly expressed in cancer cells may be a potential target for cancer therapy. We developed an E1B-55 kDa-deleted adenovirus, designated Ad.9OC, driven by nine copies of Oct-3/4 response element for treating Oct-3/4-expressing metastatic bladder cancer.
Experimental Design:
We examined the expression of Oct-3/4 in human bladder tumor tissues and bladder cancer cell lines. We also evaluated the cytolytic and antitumor effects of Ad.9OC on bladder cancer cells in vitro and in vivo.
Results:
Oct-3/4 expression was detected in bladder cancer cell lines, as well as in human bladder tumor tissues. Notably, Oct-3/4 expression was higher in metastatic compared with nonmetastatic bladder cancer cells. Ad.9OC induced higher cytolytic activity in metastatic bladder cancer cells than in their nonmetastatic counterparts, whereas it did not cause cytotoxicity in normal cells. Pharmacologic and short hairpin RNA-mediated Oct-3/4 inhibition rendered bladder cancer cells more resistant to Ad.9OC-induced cytolysis. Replication of Ad.9OC was detected in murine bladder cancer cells and bladder tumor tissues. We also showed the effectiveness of Ad.9OC for treating bladder cancer in subcutaneous, as well as metastatic, bladder tumor models.
Conclusions:
Ad.9OC may have therapeutic potential for treating Oct-3/4-expressing tumors. Especially, metastatic bladder tumors are good target for Ad.9OC treatment. Because Oct-3/4 is expressed in a broad spectrum of cancers, Ad.9OC may be broadly applicable.
Insights
This study introduces Ad.9OC, a novel oncolytic adenovirus targeting Oct-3/4-expressing metastatic bladder cancer. Ad.9OC shows promise in selectively destroying metastatic tumors while sparing normal cells, offering a new therapeutic avenue.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Gene therapy
Background:
- Oncolytic adenoviruses selectively replicate in tumors, but targeting metastasis remains challenging.
- Oct-3/4, a marker for embryonic stem cells and tumor cells, is highly expressed in many cancers, presenting a potential therapeutic target.
- Metastatic bladder cancer requires novel treatment strategies due to limitations in current therapies.
Purpose of the Study:
- To develop and evaluate Ad.9OC, an oncolytic adenovirus engineered to target Oct-3/4-expressing metastatic bladder cancer.
- To assess the selective replication and cytolytic activity of Ad.9OC against bladder cancer cells.
- To investigate the therapeutic efficacy of Ad.9OC in preclinical models of bladder cancer metastasis.
Main Methods:
- Examined Oct-3/4 expression in human bladder tumor tissues and cell lines.
- Evaluated Ad.9OC's cytolytic and antitumor effects in vitro and in vivo.
- Assessed Ad.9OC replication in tumor cells and tissues, and its efficacy in subcutaneous and metastatic bladder tumor models.
Main Results:
- Oct-3/4 expression was confirmed in bladder cancer tissues and cell lines, with higher levels in metastatic cases.
- Ad.9OC demonstrated significant cytolytic activity against metastatic bladder cancer cells, sparing normal cells.
- Ad.9OC effectively treated both subcutaneous and metastatic bladder tumors in vivo, with replication observed in tumor tissues.
Conclusions:
- Ad.9OC exhibits therapeutic potential for Oct-3/4-expressing tumors, particularly metastatic bladder cancer.
- The targeted approach of Ad.9OC offers a promising strategy for combating cancer metastasis.
- Given Oct-3/4's broad expression in various cancers, Ad.9OC may have wide-ranging therapeutic applicability.
