Anti-SIRPa Monoclonal Antibody

Class

monoclonal antibody

Signal regulatory protein alpha (SIRPα) is a receptor expressed on macrophages and other myeloid cells that acts as an inhibitory checkpoint governing phagocytosis, the process by which these cells engulf and clear other cells. Its natural binding partner, CD47, is displayed on the surface of both healthy and malignant cells and functions as a 'do not eat' signal: when CD47 engages SIRPα, it delivers an inhibitory signal that restrains macrophage attack. Many tumors exploit this axis by overexpressing CD47, allowing cancer cells to evade innate immune clearance even when they carry markers that would otherwise flag them for destruction. Anti-SIRPα antibodies are designed to block this interaction from the macrophage side, disrupting the inhibitory signal and lowering the threshold for phagocytosis of antibody-coated or otherwise marked tumor cells. This approach is explored mainly in oncology, often alongside antibodies that tag tumor cells for destruction, since removing the 'do not eat' brake can amplify the effect of such tagging. Because SIRPα is restricted largely to myeloid lineage cells rather than being broadly expressed like CD47, targeting SIRPα directly is one strategy intended to reduce the sequestration of drug by red blood cells that can complicate CD47-directed approaches.