Antibody mediated blockade of phosphatidylserine to enhance immune checkpoint blockade by repolarizing immune suppressive mechanisms of the tumor microenvironment.

e23195Background: The expression of phosphatidylserine (PS) on cell surfaces drives immunosuppressive mechanisms associated with tolerogenic cell death. In the tumor microenvironment, PS is exposed on tumor cells and tumor vascular endothelial cells and is further exposed with conventional anti-neoplastic therapies. PS signals through multiple immune cell signaling receptors where it drives the expansion of myeloid-derived suppressor cells (MDSCs), regulatory T cells, M2 macrophages, and stimulates the production of immunosuppressive cytokines. PS targeting antibodies have significant anti-tumor effects in multiple preclinical tumor models to re-activate the immune response in the tumor microenvironment. Methods: The combination of PS-targeting antibody ch1N11 with anti-PD-1 or anti-PD-L1 antibodies was compared to single agent therapy in E0771 and EMT-6 mouse syngeneic breast tumor models. Mice were treated IP up to twice per week with ch1N11, anti-PD-1, or anti-PD-L1 as single agents or combinations of ...