Checkpoint blockade inhibitors enhances the effectiveness of a Listeria monocytogenes-based melanoma vaccine

Abstract

Melanoma continues to be a significant health concern worldwide despite recent improvements in treatment. Unlike many other prominent cancers, melanoma incidence in both men and women increased over the past decade in the U. S. and much of the developed world. The single greatest risk factor for melanoma is damage from ultraviolet radiation associated with lifestyle. The lifestyle component suggests that although melanoma risk can be minimized with behavioral changes, vaccinating high-risk individuals against melanoma may be the most efficacious preventative method. Accordingly, using a highly attenuated, double-mutant L. monocytogenes strain expressing a tumor-associated antigen, we obtained significant protection against melanoma in a mouse model. The Listeria-based vaccine induced protection through antigen-specific CD8+ T-cells inducing both a protective primary and a memory T-cell response. Vaccinated animals were significantly protected from melanoma. When used in conjunction with checkpoint blockade treatment, the vaccine substantially reduced tumor size and number relative to animals receiving checkpoint blockade (CPB) alone. This study provides evidence that CPB treatment synergizes with a L. monocytogenes-based melanoma vaccine to enhance vaccine-mediated protection.