Immune-mediated cure of established B16F10 melanoma with a nonvirulent strain of Toxoplasma gondii (162.12)

Abstract

Abstract Immune recognition and elimination of tumors protects us from cancer. Tumors frequently manifest immunosuppressive mechanisms to avoid anti-tumor immunity and thereby become clinical challenges. The immune system is quite sensitive to microbial pathogens and microbes or microbial extracts are very effective adjuvants to stimulate an immune response. Here we present the results of treatment of established cutaneous B16F10 murine melanoma by intratumoral injection of a fully attenuated uracil auxotroph strain of Toxoplasma gondii (ΔCPS) that cannot replicate in vivo. ΔCPS exposure breaks immunosuppression and stimulates a strong Th1 antitumor immune response in vivo that cures established primary melanoma and develops immune memory that confers protection against subsequent rechallenges. This treatment modifies the tumor microenvironment, increases MHC Class I expression on tumor cells and reverses immunosuppression, permitting a tumor-antigen specific CD8 T cell response to eliminate the tumor. The approach has efficacy against multiple tumor types and has potential for clinical utility.