Definition

A humanized monoclonal antibody targeting the cell surface protein CD24, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-CD24 monoclonal antibody ATG-031 targets and binds to CD24 expressed on tumor cells, thereby blocking the interaction of CD24 with sialic acid-binding Ig-like lectin 10 (Siglec-10) expressed on innate immune cells including tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). This prevents CD24/Siglec-10-mediated signaling and abrogates the CD24/Siglec-10-mediated inhibition of macrophage-mediated phagocytosis of tumor cells. This results in macrophage-dependent tumor cell phagocytosis, repolarization from the immunosuppressive M2 subtype macrophages to the anti-tumor M1 subtype in the TME, and the abrogation of the immunosuppressive TME. CD24, a glycophosphatidylinositol (GPI)-anchored, highly glycosylated cell adhesion protein, is overexpressed on the surface of a variety of cancer cells. Expression of CD24, and its interaction with Siglec-10, protects cancer cells from phagocytosis, thereby allowing cancer cells to proliferate.