Simpson, GR, Horvath, A, Annels, NE et al. (10 more authors) (2012) Combination of a fusogenic glycoprotein, pro-drug activation and oncolytic HSV as an intravesical therapy for superficial bladder cancer. British Journal of Cancer, 106. pp. 496-507. ISSN 0007-0920
Abstract
Background: There are still no effective treatments for superficial bladder cancer (SBC)/non-muscle invasive bladder cancer. Following treatment, 20% of patients still develop metastatic disease. Superficial bladder cancer is often multifocal, has high recurrences after surgical resection and recurs after intravesical live Bacillus Calmette-Guérin. Oncovex GALV/CD, an oncolytic herpes simplex virus-1, has shown enhanced local tumour control by combining oncolysis with the expression of a highly potent pro-drug activating gene and the fusogenic glycoprotein. Methods: In vitro fusion/prodrug/apoptotic cell-based assays. In vivo orthotopic bladder tumour model, visualised by computed microtomography. Results: Treatment of seven human bladder carcinoma cell lines with the virus resulted in tumour cell killing through oncolysis, pro-drug activation and glycoprotein fusion. Oncovex GALV/CD and mitomycin C showed a synergistic effect, whereas the co-administration with cisplatin or gemcitabine showed an antagonistic effect in vitro. Transitional cell cancer (TCC) cells follow an apoptotic cell death pathway after infection with Oncovex GALV/CD + with or without 5-FC. In vivo results showed that intravesical treatment with Oncovex GALV/CD prodrug (5-FC) reduced the average tumour volume by over 95% compared with controls.Discussion: Our in vitro and in vivo results indicate that Oncovex GALV/CD can improve local tumour control within the bladder, and potentially alter its natural history.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2012, Cancer Research UK. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
Keywords: | Oncolytic HSV; Bladder cancer; Micro CT; Orthotopic model; Fusogenic glycoprotein; Prodrug therapy |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Oncology and Cancer Research - Labs (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 25 Aug 2016 15:13 |
Last Modified: | 01 Mar 2019 11:49 |
Published Version: | http://dx.doi.org/10.1038/bjc.2011.577 |
Status: | Published |
Publisher: | Cancer Research UK |
Identification Number: | 10.1038/bjc.2011.577 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:87599 |