anti-CD47 monoclonal antibody IMC-002

A human immunoglobulin G4 (IgG4) monoclonal antibody targeting leukocyte surface antigen CD47, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-CD47 monoclonal antibody IMC-002 targets and binds to CD47 expressed on tumor cells, blocking the interaction of CD47 with signal regulatory protein alpha (SIRPa) expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of macrophage activation and phagocytosis of cancer cells. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1), which is expressed on macrophages, and results in macrophage activation and the specific phagocytosis of tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSCs) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, thereby allowing cancer cells to proliferate. IMC-002 does not bind to red blood cells (RBCs). This may prevent adverse effects such as anemia that can result from the blockade of CD47 expressed on RBCs.