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Updated: May 11, 2025
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Oncolytic virotherapy provides a potent therapy option for squamous bladder cancer
Julia Pannhausen1,2, Julia Wirtz1,2, Klaus Mantwill3
1Institute of Pathology, Uniklinik RWTH Aachen, 52074, Aachen, Germany.
Abstract:
Prognosis for squamous cell carcinoma (SCC) of the bladder is limited mostly because of lack of effective treatment regimens. Oncolytic virotherapy represents a promising option for bladder cancer and received in 2024 FDA therapy designation for the treatment of non-invasive high-grade bladder cancer (BLCA). For muscle-invasive bladder cancer (MIBC), preclinical studies demonstrated high efficacy of the oncolytic adenovirus XVir-N-31 in urothelial carcinoma (UC). We analyzed the potency of XVir-N-31 virotherapy as a novel treatment option in SCC. Replication of XVir-N-31 has been described to be facilitated by high expression level of Y-Box binding protein 1 (YB-1). Increased YB-1-mRNA expression was detected in basal/squamous subtype in TCGA BLCA cohort compared to urothelial and luminal BLCA and correlated with patient outcomes. Furthermore, immunohistochemical staining of 89 SCC on a tissue microarray confirmed strong YB-1 expression in squamous BLCA (sq-BLCA). In vitro, XVir-N-31 showed in subtype-specific cell cultures high rates of infection, replication and cell-killing capacity. In a novel in ovo xenograft model, XVir-N-31 impaired growth of xenografts of patient-derived ex vivo cell lines (p-SCC, p-UC) with growth suppression rates of 39-49%. We provide preclinical evidence ex vivo and in ovo for high efficacy of XVir-N-31 based oncolytic virotherapy as novel SCC therapy.
Insights
Oncolytic virotherapy with adenovirus XVir-N-31 shows promise for treating bladder squamous cell carcinoma (SCC). Preclinical studies confirm its efficacy in targeting SCC by leveraging Y-Box binding protein 1 (YB-1) expression.
Area of Science:
- Oncolytic virotherapy
- Bladder cancer research
- Squamous cell carcinoma (SCC) treatment
Background:
- Limited effective treatment options for bladder squamous cell carcinoma (SCC) impact patient prognosis.
- Oncolytic virotherapy is a promising approach for bladder cancer, with FDA designation for non-invasive high-grade bladder cancer (BLCA).
- Preclinical studies show efficacy of oncolytic adenovirus XVir-N-31 in urothelial carcinoma (UC), but its potential in SCC is unexplored.
Purpose of the Study:
- To evaluate the efficacy of oncolytic adenovirus XVir-N-31 as a novel treatment for bladder squamous cell carcinoma (SCC).
- To investigate the role of Y-Box binding protein 1 (YB-1) in facilitating XVir-N-31 replication in SCC.
Main Methods:
- Analyzed YB-1 mRNA expression in TCGA BLCA cohort and correlated it with patient outcomes.
- Performed immunohistochemical staining for YB-1 in 89 SCC samples.
- Assessed XVir-N-31 infection, replication, and cell-killing capacity in vitro in subtype-specific cell cultures.
- Evaluated XVir-N-31 efficacy in a novel in ovo xenograft model using patient-derived SCC and UC cell lines.
Main Results:
- Increased YB-1 mRNA expression was detected in the basal/squamous subtype of BLCA, correlating with patient outcomes.
- Strong YB-1 expression was confirmed in squamous BLCA (sq-BLCA) via immunohistochemistry.
- XVir-N-31 demonstrated high infection, replication, and cell-killing rates in vitro.
- In ovo xenografts showed significant growth suppression (39-49%) by XVir-N-31.
Conclusions:
- Preclinical data support the high efficacy of XVir-N-31 oncolytic virotherapy for bladder squamous cell carcinoma (SCC).
- YB-1 expression is a potential biomarker for XVir-N-31 therapy in SCC.
- XVir-N-31 represents a promising novel therapeutic strategy for SCC of the bladder.
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