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Mol Ther Oncolytics. 2018 Feb 14;9:1-12. doi: 10.1016/j.omto.2018.02.001. eCollection 2018 Jun 29.

Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus.

Author information

1
Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, Leggett Building, Daphne Jackson Road, University of Surrey, Guildford GU2 7WG, UK.
2
The Institute of Cancer Research, London SM2 5PT, UK.
3
Viralytics Limited, Suite 305, Level 3, 66 Hunter Street, Sydney, NSW 2000, Australia.
4
Section of Experimental Oncology, Leeds Institute of Cancer and Pathology, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
5
Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA.

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.

KEYWORDS:

bladder cancer; coxsackievirus A21; intercellular adhesion molecule-1

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