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Updated: Oct 1, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Epidermal growth factor receptor targeting of replication competent adenovirus enhances cytotoxicity in bladder
H G van der Poel1, B Molenaar, V W van Beusechem
1Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Purpose:
We evaluated the delivery and oncolytic potential of targeted replication competent adenoviruses in bladder cancer lines.
Materials And Methods:
Seven established human bladder cancer tumor lines (5637, SW800, TCCsup, J82, Scaber, T24 and 253J) were studied for the expression of integrins alpha(v)beta3, alpha(v)beta5, Coxsackievirus and adenovirus receptor, epidermal growth factor receptor (EGF-R) and epithelial cell adhesion molecule antigens using flow cytometry analysis. Bispecific single chain Fv fragments were used to target replication deficient luciferase reporter adenovirus to EGF-R (425-s11) or to epithelial cell adhesion molecule (C28-s11) antigens. Moreover, a fiber modified adenovirus targeting alpha(v)-integrins was studied. Replication competent serotype-5 adenoviruses attenuated to replicate specifically in retinoblastoma pRb (Ad5-d24) or p53 deficient (Ad5-d55K) cells were tested in vitro for oncolytic properties.
Results:
Low to absent Coxsackievirus and adenovirus receptor expression was found in 5 of the 7 tumor lines (SW800, J82, T24, 5637 and Scaber). EGF-R expression was found in all cell lines, whereas elevated epithelial cell adhesion molecule expression was seen in 3 (5637, Scaber and TCCsup), alpha(v)beta3-integrin was found in 1 (Scaber) and alpha(v)beta5-integrin was found in 3 (TCCsup, 253J and T24). EGF-R targeting using 425-s11 improved transgene expression in all cell lines from 2.1 to 12.5 times over nontargeted viruses. Epithelial cell adhesion molecule and integrin targeting was inferior to EGF-R targeting with a maximal increase in transgene expression of 2 times for epithelial cell adhesion molecule in 5637cells and 1.6 times for integrin targeting in T24 cells. Comparison of the wild-type replication competent virus with conditionally replicating adenoviruses (Ad5-d55K and Ad5-d24) showed superior oncolytic activity for the latter 2 in all lines. Furthermore, improved cytotoxicity (29% to 33%) was obtained in 4 of the 7 lines after pre-incubation of Ad5-d24 with 425-s11.
Conclusions:
EGF-R directed bispecific single chain antibodies enhance adenovirus mediated transgene expression and oncolysis in bladder cancer lines.
Insights
Targeted adenoviruses show potential for bladder cancer treatment. Epidermal Growth Factor Receptor (EGF-R) targeting improved adenovirus delivery and oncolytic effects in bladder cancer cells.
Area of Science:
- Oncolytic virology
- Cancer gene therapy
- Bladder cancer research
Background:
- Bladder cancer remains a significant health challenge.
- Targeted viral therapies offer a promising avenue for cancer treatment.
- Adenoviruses are being explored for their oncolytic potential in various cancers.
Purpose of the Study:
- To evaluate the efficacy of targeted replication-competent adenoviruses in bladder cancer cell lines.
- To assess the delivery and oncolytic capabilities of adenoviruses engineered to target specific cancer antigens.
Main Methods:
- Seven human bladder cancer cell lines were analyzed for antigen expression (EGF-R, EpCAM, integrins, CAR).
- Bispecific antibodies were used to target adenoviruses to EGF-R and EpCAM.
- Fiber-modified adenoviruses targeted integrins.
- Replication-competent adenoviruses (Ad5-d24, Ad5-d55K) were tested for oncolytic activity.
Main Results:
- EGF-R was expressed in all tested bladder cancer lines.
- Targeting EGF-R significantly enhanced adenovirus-mediated transgene expression (2.1-12.5 fold).
- Conditionally replicating adenoviruses demonstrated superior oncolytic activity compared to wild-type virus.
- Combining EGF-R targeting with Ad5-d24 improved cytotoxicity in several cell lines.
Conclusions:
- EGF-R directed targeting enhances adenovirus-mediated transgene expression and oncolysis in bladder cancer.
- Targeted oncolytic adenoviruses represent a potential therapeutic strategy for bladder cancer.
- Further research is warranted to optimize these therapies for clinical application.
