Abstract A36: Treatment of established dermal murine B16F10 melanoma with an attenuated Toxoplasma gondii eliminates the treated tumor and stimulates systemic antitumor immunity.

Abstract

Abstract While the surgical removal of dermal melanoma cures that lesion, it does nothing to stimulate antitumor immunity that could potentially identify and eliminate occult metastatic disease. An immune based treatment that eliminates the primary dermal melanoma could also potentially generate systemic immunity that will protect against metastatic disease. We have utilized an attenuated strain of Toxoplasma gondii (cps) to break tumor-mediated immunosuppression, stimulate an antitumor immune response that eliminates the dermal tumor, and generate systemic antitumor immunity that leads to rejection of subsequent dermal or intravenous challenges with B16F10. T. gondii is an obligate intracellular eukaryotic parasite that infects virtually any mammalian species. The cps strain is a uracil auxotroph that can be grown in vitro but is unable to replicate in vivo. Despite its lack of infectivity, it enters cells and stimulates a strong T-cell mediated immune response characterized by long lasted CD8 effector cells. The presence of cps in the tumor microenvironment modifies the phenotype of tumor infiltrating leukocytes, and along with the expected anti-Toxoplasma immune response there is antigen-spreading so that tumor antigens are responded to and the immune system recognizes subsequent tumor challenges when there is no associated cps. The treatment requires CD8 and NK cells for efficacy but does not require CD4 cells. The treatment also requires that the host express IL-12 and Ifn-g. The treatment requires live cps for efficacy and is effective in mice that are latently infected with another strain of T. gondii, so it could function in the high percentage of humans with latent T. gondii infection and an established immune response against T. gondii. Citation Format: Steven Fiering, Jason R. Baird, Katelyn Byrne, Patrick Lizotte, David Mullins, Mary Jo turk. Treatment of established dermal murine B16F10 melanoma with an attenuated Toxoplasma gondii eliminates the treated tumor and stimulates systemic antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A36.