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Updated: Aug 5, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 2, 2013
Optimization of the MB49 mouse bladder cancer model for adenoviral gene therapy
A Loskog1, C Ninalga, T Hedlund
1Clinical Immunology Division, Rudbeck Laboratory, Uppsala University, Sweden. angelica.loskog@klinimm.uu.se
Abstract:
Bladder cancer is regarded as a promising candidate for innovative therapies in the field of immune and gene therapy. In this paper, we present the subcutaneous, metastatic and a novel orthotopic model of murine MB49 bladder cancer in C57BL/6 mice. We further show the potential of using adenoviral vectors together with different transduction enhancers to augment in vivo gene delivery. Finally, we present candidate genes for tumour detection, therapy or targeting. The MB49 tumour grew rapidly in mice. The subcutaneous model allowed for tumour detection within a week and the possibility to monitor growth rate on a day-by-day basis. Injection of MB49 cells intravenously into the tail vein gave rise to lung metastases within 16 days, while instillation of tumour cells into pretreated bladders led to a survival time of 20-40 days. Adenoviral vectors can be used as a vehicle for gene transfer to the bladder. By far, the most potent transduction enhancer was Clorpactin, also known as oxychlorosene. Last, we show that MB49 cells express tumour-associated antigens like bladder cancer-4, prostate stem cell antigen and six-transmembrane epithelial antigen of the prostate. Given the possibility for efficient genetic modification of the bladder and the presence of known tumour antigens, the MB49 models can be used in innovative ways to explore immunogene therapy.
Insights
New mouse models for bladder cancer (MB49) enable testing of gene and immune therapies. Researchers found Clorpactin effective for gene delivery, identifying potential targets for innovative bladder cancer treatments.
Area of Science:
- Oncology
- Immunotherapy
- Gene Therapy
- Animal Models
Background:
- Bladder cancer presents opportunities for novel immune and gene therapies.
- Development of robust preclinical models is crucial for advancing bladder cancer research.
Purpose of the Study:
- To establish and characterize subcutaneous, metastatic, and orthotopic MB49 bladder cancer models in mice.
- To evaluate adenoviral vectors and transduction enhancers for in vivo gene delivery to the bladder.
- To identify candidate genes and tumor antigens for bladder cancer detection, therapy, and targeting.
Main Methods:
- Establishment and characterization of subcutaneous, intravenous (metastatic), and orthotopic MB49 bladder cancer models in C57BL/6 mice.
- Assessment of adenoviral vectors for gene transfer efficiency in the bladder, utilizing various transduction enhancers.
- Analysis of MB49 cell expression of known tumor-associated antigens (e.g., bladder cancer-4, prostate stem cell antigen).
Main Results:
- The MB49 model demonstrated rapid tumor growth, allowing for early detection and daily monitoring in subcutaneous settings.
- Intravenous injection led to lung metastases within 16 days; orthotopic models yielded a survival of 20-40 days.
- Clorpactin (oxychlorosene) emerged as a highly potent transduction enhancer for adenoviral gene delivery to the bladder.
- MB49 cells express key tumor antigens, including bladder cancer-4, prostate stem cell antigen, and six-transmembrane epithelial antigen of the prostate.
Conclusions:
- The developed MB49 mouse models are suitable for studying bladder cancer progression and evaluating therapeutic strategies.
- Adenoviral vectors, enhanced by Clorpactin, provide an effective means for gene delivery in the bladder.
- The identified tumor antigens and established models support the exploration of innovative immunogene therapies for bladder cancer.
