Abstract B21: Immune-based treatment of ovarian cancer in a mouse model with attenuated Toxoplasma gondii.

Ovarian cancer is generally diagnosed at stage 3 or 4 metastatic disease. The disease course of ovarian cancer is characterized by a remission period following surgery and chemotherapy, but the remission generally only lasts 1-2 years and the relapse is very difficult to treat, so the disease has very poor 5 year survival rates. Effective stimulation of an antitumor immune response during the remission period could eliminate occult metastatic disease and therefore developing immunotherapy approaches for ovarian cancer that can be applied during the remission period is of considerable interest. We have utilized the ID8 based ovarian cancer model in the form of the highly aggressive ID8/Vegf/Defb29 subline to test the ability of an attenuated strain of T. gondii (cps) to stimulate an anti-tumor immune response. We show that following establishment of the tumor by IP injection of tumor cells, introduction of cps into the peritoneal cavity significantly slows the development of the disease. cps predominantly invades immunosuppressive phagocytes in the tumor microenvironment and modifies these and newly recruited phagocytes to be immunostimulatory. The phagocytes are now much more efficient antigen processers and presenters, the immune system is freed from immunosuppression, and the antitumor immune response is activated. The treatment efficacy is associated with a large increase of tumor antigen-specific CD8 T cells and these T cells demonstrate antitumor activity in a transfer experiment and tumor challenge. cps is nontoxic, even in animals with no adaptive immune system, and is a fully attenuated but highly effective platform for developing cancer treatment vaccines. Further developed and applied, cps could be the basis for an autologous tumor vaccine approach that has the potential to improve ovarian cancer outcomes.

Citation Format: Steven Fiering, Jason R. Baird, Barbara Fox, Patrick Lizotte, Kiah Sanders, Jose Conjeo-Garcia, David Bzik. Immune-based treatment of ovarian cancer in a mouse model with attenuated Toxoplasma gondii. [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 B21.