Delivery of Macrophage Activating Nanoparticles and Checkpoint Inhibitors Improves Melanoma Immunotherapy in Mice

Abstract The immune system clears tumors from forming in the body by first activating the innate immune system, which subsequently triggers the adaptive immune system to mount robust responses against cancer cells. This strategy involves initially activating phagocytic immune cells, such as dendritic cells and macrophages, followed by the reinvigoration of adaptive immune cells, like T cells, to develop effective immune responses against tumors. Herein, the one‐two punch strategy is utilized of first activating the innate immune system with biomaterial‐based adjuvants composed of succinate polymers and then introducing checkpoint inhibitor anti‐PD1 to enhance the adaptive immune response. Specifically, polyethylene succinate nanoparticles (PES NPs) are generated from succinate‐based polymers. These nanoparticles induced the activation of mouse‐derived dendritic cells and peritoneal macrophages in vitro. When administered intravenously in B16BL6 melanoma tumor‐bearing C57BL/6J mice, PES NPs accumulate and activate macrophages within the tumor microenvironment (TME). Furthermore, infusion of PES NPs and anti‐PD1 antibody treatment in B16BL6 tumor‐bearing mice resulted in reduced tumor burden. Collectively, these findings suggest that sequential activation of innate and then adaptive immune cells is beneficial for developing cancer immunotherapies.