Annels, NE, Arif, M, Simpson, GR et al. (11 more authors) (2018) Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus. Molecular Therapy - Oncolytics, 9. C. pp. 1-12. ISSN 2372-7705
Abstract
As a clinical setting in which local live biological therapy is already well established, non-muscle invasive bladder cancer (NMIBC) presents intriguing opportunities for oncolytic virotherapy. Coxsackievirus A21 (CVA21) is a novel intercellular adhesion molecule-1 (ICAM-1)-targeted immunotherapeutic virus. This study investigated CVA21-induced cytotoxicity in a panel of human bladder cancer cell lines, revealing a range of sensitivities largely correlating with expression of the viral receptor ICAM-1. CVA21 in combination with low doses of mitomycin-C enhanced CVA21 viral replication and oncolysis by increasing surface expression levels of ICAM-1. This was further confirmed using 300-μm precision slices of NMIBC where levels of virus protein expression and induction of apoptosis were enhanced with prior exposure to mitomycin-C. Given the importance of the immunogenicity of dying cancer cells for triggering tumor-specific responses and long-term therapeutic success, the ability of CVA21 to induce immunogenic cell death was investigated. CVA21 induced immunogenic apoptosis in bladder cancer cell lines, as evidenced by expression of the immunogenic cell death (ICD) determinant calreticulin, and HMGB-1 release and the ability to reject MB49 tumors in syngeneic mice after vaccination with MB49 cells undergoing CVA21 induced ICD. Such CVA21 immunotherapy could offer a potentially less toxic, more effective option for the treatment of bladder cancer.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2018, Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC BY-NC-ND 4.0) |
Keywords: | bladder cancer; coxsackievirus A21; intercellular adhesion molecule-1 |
Dates: |
|
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) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L376PA |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Jul 2018 12:38 |
Last Modified: | 25 Jun 2023 21:26 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.omto.2018.02.001 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:133510 |