IBCN 2022: ICAM-1 Targeted Immunotherapeutic Coxsackievirus A21 (CVA21) as an Oncolytic Agent for Non-Muscle Invasive Bladder Cancer

(UroToday.com) Following the overview of Oncolytic Virotherapy (OV), Dr. Pandha described a strategy using a coxsackie A21 virus in the treatment of bladder cancer. CAVATAK is a single stranded naked RNA virus that attaches to and internalized into the tumor cells via the ICAM-1 receptor. It functions via the dual oncolytic pathway through both direct oncolysis and the ensuing immunogenic response. Dr. Pandha concentrated his discussion on the clinical trial carried out using intravesical treatment of newly diagnosed non-muscle invasive bladder cancer (NMIBC) patients.

In vitro work early on demonstrated selective killing of certain cancer cell lines, including T24, TCCSUP, S637, but not others, such as KU19-19, VMCUB, and RT112. Not surprisingly, cytotoxicity depends on the expression of ICAM on the different cell lines, with those highly expressing the receptor more prone to viral attack. Following successful animal experiments, a clinical trial called the CANON study was carried out, using 5 daily doses of CAVATAK administered intravesically, followed by TUR of the tumor at day 8.¹  From the urine cytokine assay, there was evidence of immunogenic cell death as the levels of HMGB1 was found to be elevated following treatment. Oncolytic virotherapy also resulted in the induction of IFN genes and immune checkpoint blockade. Clinically, the investigators witnessed several partial and complete responses following treatment.

Presented by:  Hardev Pandha, MD, PhD, Professor of Medical Oncology, University of Surrey

Written by: Roger Li, Urologic Oncologist, Moffitt Cancer Center, during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain