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Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus

Annels, Nicola, Arif, Mehreen, Simpson, Guy, Denyer, Mick, Moller-Levet, Carla, Mansfield, David, Butler, Rachel, Shafren, Darren, Au, Gough, Knowles, Margaret , Harrington, Kevin, Vile, Richard, Melcher, Alan and Pandha, Hardev (2018) Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus Molecular Therapy - Oncolytics, 9. pp. 1-12.

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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.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Annels, NicolaN.Annels@surrey.ac.uk
Arif, Mehreenm.arif@surrey.ac.uk
Simpson, GuyG.Simpson@surrey.ac.uk
Denyer, MickM.Denyer@surrey.ac.uk
Moller-Levet, CarlaC.Moller-Levet@surrey.ac.uk
Mansfield, David
Butler, RachelR.Shrimpton@surrey.ac.uk
Shafren, Darren
Au, Gough
Knowles, Margaret
Harrington, Kevin
Vile, Richard
Melcher, Alan
Pandha, HardevH.Pandha@surrey.ac.uk
Date : 14 February 2018
DOI : 10.1016/j.omto.2018.02.001
Copyright Disclaimer : © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Depositing User : Melanie Hughes
Date Deposited : 13 Nov 2018 10:34
Last Modified : 13 Nov 2018 10:34
URI: http://epubs.surrey.ac.uk/id/eprint/849859

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