Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus

Nicola E. Annels, Mehreen Arif, Guy R. Simpson, Mick Denyer, Carla Moller-Levet, David Mansfield, Rachel Butler, Darren Shafren, Gough Au, Margaret Knowles, Kevin Harrington, Richard Vile, Alan Melcher, Hardev Pandha

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalMolecular Therapy - Oncolytics
Volume9
DOIs
StatePublished - Jun 29 2018

Keywords

  • bladder cancer
  • coxsackievirus A21
  • intercellular adhesion molecule-1

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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    Annels, N. E., Arif, M., Simpson, G. R., Denyer, M., Moller-Levet, C., Mansfield, D., Butler, R., Shafren, D., Au, G., Knowles, M., Harrington, K., Vile, R., Melcher, A., & Pandha, H. (2018). Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus. Molecular Therapy - Oncolytics, 9, 1-12. https://doi.org/10.1016/j.omto.2018.02.001