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Updated: Jun 3, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Increased antitumor capability of fiber-modified adenoviral vector armed with TRAIL against bladder cancers
Youguang Zhao1, Ying Li, Qingtang Wang
1Department of Urology, General Hospital of Chengdu Military Area Command of Chinese PLA, Chengdu, 610083 Sichuan Province, People's Republic of China. zhaoyg717@163.com
Abstract:
Adenoviral vectors are widely used for cancer therapy and show a tumor-suppressing effect. However, bladder cancers are found to be resistant against infection of Ad5-derived adenoviral vector, limiting the application of the existing strategy of gene therapy. Therefore, efforts to develop novel types of adenoviral vector aimed for improving the viral infection and enhancing expression level of tumor-inhibiting transgene is urgently required. We constructed a 5/35 fiber-modified E1A-deleted adenoviral vector armed with TRAIL gene. Its ability to express this gene for inhibition of bladder cancer cell growth was investigated in our work. The results showed that this modification in fiber region facilitates adenoviral infection to bladder cancer, perhaps due to high expression of CD46 on target cell surface. Subsequently, we found an enhanced expression level of TRAIL mediated by 5/35 fiber-modified adenoviral vectors in bladder cancer cells, leading to an increased tumor-inhibiting capability of 5/35 adenoviral vector against bladder cancer cells. Consistently, growth of xenograft tumors in mice was also effectively inhibited by 5/35 fiber-modified vector-mediated gene therapy strategy. The 5/35 fiber-modified adenoviral vector-based gene transfer shows an improved efficacy against bladder cancers. The application of this novel gene therapy vector may benefit the patients in clinical bladder cancer treatment.
Insights
Novel adenoviral vectors overcome resistance in bladder cancer gene therapy. A 5/35 fiber modification enhances viral infection and TRAIL gene expression, effectively inhibiting tumor growth in preclinical models.
Area of Science:
- Oncolytic Virotherapy
- Gene Therapy
- Cancer Research
Background:
- Adenoviral vectors are utilized in cancer therapy but face challenges with bladder cancer infection.
- Resistance in bladder cancers to Ad5-derived vectors limits current gene therapy applications.
- Development of modified adenoviral vectors is crucial for enhanced infection and therapeutic gene expression.
Purpose of the Study:
- To engineer a novel adenoviral vector for improved bladder cancer gene therapy.
- To evaluate the efficacy of a 5/35 fiber-modified adenoviral vector carrying the TRAIL gene against bladder cancer.
- To assess the vector's potential for clinical application in bladder cancer treatment.
Main Methods:
- Construction of an E1A-deleted adenoviral vector with a 5/35 fiber modification.
- Arming the vector with the TRAIL (TNF-related apoptosis-inducing ligand) gene.
- In vitro assessment of viral infection, gene expression, and cancer cell growth inhibition.
- In vivo evaluation of tumor growth inhibition in xenograft mouse models.
Main Results:
- The 5/35 fiber modification enhanced adenoviral vector infection in bladder cancer cells, potentially via CD46 expression.
- Enhanced expression of the TRAIL transgene was observed in bladder cancer cells using the modified vector.
- The 5/35 fiber-modified vector demonstrated increased tumor-inhibiting capability against bladder cancer cells.
- Significant inhibition of xenograft tumor growth was achieved in vivo with this gene therapy strategy.
Conclusions:
- The 5/35 fiber-modified adenoviral vector represents an improved platform for bladder cancer gene therapy.
- This novel vector design enhances viral entry and therapeutic payload delivery, leading to effective tumor suppression.
- The findings suggest promising clinical potential for this gene therapy approach in treating bladder cancers.
