Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy

SIMPLE SUMMARY: Viruses are being explored as a treatment strategy for cancer by exploiting their ability to infect and kill malignant cells. Viruses also engage the immune system to promote the recognition and clearance of tumors from the body. A major concern with using viruses for therapy is anti-viral immunity, which could clear the virus before it can promote an anti-tumor response. We aim to determine the extent to which anti-viral immunity affects anti-tumor immunity. Our findings suggest that anti-viral immunity does not mitigate the anti-cancer effects of viral infection. Thus, virus therapy may be a valid treatment strategy, even in individuals that have pre-existing immunity to the virus. ABSTRACT: Oncolytic viruses (OVs) are being developed as a type of immunotherapy and have demonstrated durable tumor responses and clinical efficacy. One such OV, Coxsackievirus A21 (CVA21), exhibited therapeutic efficacy in early phase clinical trials, demonstrating the ability to infect and kill cancer cells and stimulate anti-tumor immune responses. However, one of the major concerns in using this common cold virus as a therapeutic is the potential for innate and adaptive immune responses to mitigate the benefits of viral infection, particularly in individuals that have been exposed to coxsackievirus prior to treatment. In this study, we assess melanoma responses to CVA21 in the absence or presence of prior exposure to the virus. Melanomas were transplanted into naïve or CVA21-immunized C57BL6 mice and the mice were treated with intratumoral (IT) CVA21. We find that prior exposure to CVA21 does not dramatically affect tumor responses, nor does it alter overall survival. Our results suggest that prior exposure to coxsackievirus is not a critical determinant of patient selection for IT CVA21 interventions.