Abstract

Reshaping immunotherapy landscape.

Cancer thrives by preventing the immune system from targeting tumor cells. While current immunotherapies use dendritic cells to activate T-cells towards specific tumor antigens, they remain expensive and of variable efficiency against tumor immunosuppressive environment. To address these issues, our team mainly focused on engineering a S. cerevisiae yeast immunotherapy that was ultimately tested in vivo on mice presenting melanoma.

Three complementary strategies were combined: First, in order to modulate the tumor environment, yeast secreting immune modulators, GM-CSF and IFNgamma, were encapsulated into alginate beads and injected in tumors. Secondly, to break the immune tolerance against cancer cells, T4 and T8 lymphocytes were elicited by a yeast antigen display system. Last, to deliver cytotoxic compounds solely in the tumor environment, a yeast hypoxia bio-sensor was designed. A side project consisted in engineering E. coli to drive MAIT lymphocytes against cancer cells instead of their original targets, parasitized cells.