Anti-CD47 antibody STING agonist conjugate for activating macrophage-mediated cancer immunotherapy in tumor microenvironment

Abstract

For successful cancer immunotherapy, immuno-suppressive tumor microenvironment must be overcome. Tumor-associated macrophages have emerged as one of the attractive targets of cancer immunotherapy due to their key role in contributing to immune suppression. Although studies have been successfully targeting the CD47 protein that are overexpressed on cancers and inhibits phagocytosis of macrophages, there are limitations that it is difficult to induce adaptive immune responses. In this dissertation, to maximize the anti-tumor immune function of macrophages, synergistic effects of anti-CD47 antibody to enhance the phagocytosis and STING agonist that promote the antigen presentation of engulfing macrophages, mediate adaptive immune responses were observed. Finally, anti-CD47 antibody STING agonist conjugate was developed and the effect of activating anti-cancer immune function of macrophages were evaluated.