| Description |
Melanoma is the deadliest form of skin cancer, and the incidence of the disease continues to rise. Recent advances in immunotherapy have given hope for durable responses in a subset of patients, and extending the benefit of these therapies to unresponsive patients is an exigent need. Oncolytic viruses have great potential to treat melanoma and enhance the effects of standard-of-care immunotherapies. Infection of tumor cells induces cell lysis, driving inflammation and releasing tumor antigens to be recognized by the immune system. In this way, viruses can directly attack malignant cells and cooperate with the immune system to eliminate infected and distant lesions in the body. Furthermore, the combination of these biologics with other immunotherapies may enhance this response. Coxsackievirus A21 (CVA21) is a naturally occurring picornavirus proven to be safe and clinically efficacious in melanoma, yet questions remain for its use in patients. One of the leading concerns is whether the presence or development of antiviral immunity to CVA21 would render the virus ineffective as a treatment strategy. Our work addresses the impact of antiviral immunity on tumor responses in melanoma. In an immunocompetent murine melanoma model, CVA21 therapy was assessed in unexposed or previously exposed hosts alone or in combination with immunotherapy. Prior exposure to the virus enhanced viral clearance but did not preclude tumor regression in response to CVA21, demonstrating the efficacy of CVA21 irrespective of antiviral immunity. |
