anti-SIRPalpha Fc fusion protein

An anti-SIRPalpha Fc fusion protein is a therapeutic biologic designed to target and inhibit Signal Regulatory Protein Alpha (SIRPα), an inhibitory receptor predominantly expressed on myeloid cells such as macrophages and dendritic cells. This platform typically involves fusing a SIRPα-binding moiety—such as a monoclonal antibody variable region or the extracellular domain of its natural ligand, CD47—to an immunoglobulin Fc domain (usually IgG1 or IgG4). The primary mechanism of action is to disrupt the interaction between SIRPα and CD47 (the "don't eat me" signal), which is frequently overexpressed on the surface of cancer cells to evade immune surveillance. By blocking this checkpoint, these fusion proteins alleviate the suppression of phagocytosis, thereby promoting the engulfment and clearance of tumor cells by macrophages. This approach is being investigated in various clinical trials for both solid tumors and hematologic malignancies, often in combination with other tumor-targeting antibodies to leverage Fc-mediated effector functions like antibody-dependent cellular phagocytosis (ADCP).

Other names

anti-SIRPalpha antibodySIRPalpha antagonistSIRPalpha-targeting Fc fusionCD47-Fc fusion proteinCD-47-Fc fusion proteinCD 47-Fc fusion protein