Oncolytic immunotherapy for the treatment of non-muscle invasive bladder cancer using intravesical coxsackievirus A21

Background As a clinical setting in which local live biological therapy is already well established, nonmuscle 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. Combining CVA21 with low doses of chemotherapy (Mitomycin C) enhances CVA21 viral replication and oncolysis by increasing expression levels of ICAM1 on bladder cancer cells. As well as initiating oncolysis, oncolytic viruses can also induce immunogenic cell death (ICD) determinants which is thought to be the optimal way to trigger a tumour-specific response and crucial for long-term therapeutic success. This study set out to confirm the enhanced cytotoxicity in vitro of bladder cancer cell lines and tissues following combined treatment of mitomycin C and CVA21 and to demonstrate the induction of immunogenic cell death determinants.