Signal regulatory protein alpha (SIRPα) V1 allele (SIRPα V1)

Signal regulatory protein alpha (SIRPα), also known as CD172a, is an inhibitory receptor predominantly expressed on myeloid cells such as macrophages and dendritic cells (UniProt P78324). It plays a pivotal role in immune homeostasis by interacting with CD47, a "don't eat me" signal expressed on healthy cells and frequently overexpressed by various malignancies to evade immune surveillance (PubMed: 29305548). The SIRPα V1 allele is one of the most prevalent human polymorphisms within the extracellular IgV domain, which is the primary binding site for CD47; understanding these allelic variations is crucial for ensuring the broad efficacy of therapeutic antibodies (Sim et al., 2018). When CD47 binds to SIRPα, it triggers the phosphorylation of intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs), leading to the recruitment of SHP-1 and SHP-2 phosphatases that suppress phagocytosis (PubMed: 30633056). In cancer therapy, monoclonal antibodies and fusion proteins targeting SIRPα, such as BI 765063, are designed to disrupt this inhibitory axis, thereby restoring the ability of macrophages to engulf and destroy tumor cells (ClinicalTrials.gov: NCT03990233). Unlike CD47-targeted therapies, SIRPα-directed agents typically avoid binding to red blood cells, potentially reducing the risk of treatment-induced anemia and improving the drug's pharmacokinetic profile (PubMed: 32165434).

Other names

CD172aSHPS-1BITMFRP84PTPNS1SIRP-alpha-1SIRPα variant 1

Antagonist of the CD47-SIRPα interaction to enhance macrophage-mediated phagocytosis.