Cluster of differentiation 33 (CD33)

Cluster of differentiation 33 (CD33) is a transmembrane receptor belonging to the sialic acid-binding immunoglobulin-like lectin (Siglec) family, predominantly expressed on cells of myeloid lineage, including myeloid progenitors, monocytes, macrophages, and some granulocytes[1][3][5][7]. CD33 contains two extracellular immunoglobulin domains and an intracellular region with immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that regulate cell activation by recruiting SHP-1 and SHP-2 phosphatases, ultimately inhibiting phagocytosis and other cellular responses[1][3]. CD33 plays a role in immune modulation, including downregulation of microglial activity in the central nervous system and the inhibition of inflammatory and immune responses. It is a validated therapeutic target in acute myeloid leukemia, where monoclonal antibodies and antibody-drug conjugates targeting CD33 are used for therapy (such as gemtuzumab ozogamicin), and is being explored as a target in neurodegenerative diseases such as Alzheimer’s disease due to its regulatory role in microglia[1][4][5][7]. CD33 expression serves as a diagnostic biomarker for myeloid neoplasms and informs targeted therapy selection in leukemia[7]. Notable safety concerns with CD33-targeted therapies include myelosuppression and, as observed in earlier trials of gemtuzumab ozogamicin, increased treatment-related mortality[1][7].

Other names

Siglec-3Sialic acid-binding immunoglobulin-like lectin 3SIGLEC3gp67p67

Antibody-drug conjugate binding to CD33-expressing cells and delivering cytotoxic agents (e.g., calicheamicin); Monoclonal antibody-mediated immune cell targeting and induction of apoptosis in CD33-positive cells