Abstract
Salmonella VNP20009 inhibits tumor growth in preclinical models but its efficacy in humans is limited, potentially because cells mount an autophagy response that destroys the therapeutic bacteria. To neutralize this protective response, we combined VNP20009 with long-circulating liposomes containing the autophagy arrest agent hydroxychloroquine. This combination was associated with significantly larger numbers of intracellular Salmonella, accumulated autophagic vacuoles and much greater cell death in vitro. The combination was also associated with greater tumor-targeting ability, slower tumor growth and longer survival than free hydroxychloroquine in a murine model of melanoma. Our results suggest that combining tumor-targeting Salmonella with autophagy arrest may be effective for treating highly aggressive melanoma.