CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is atransmembrane receptor expressed on cells ofmyeloid lineage.[5] It is usually considered myeloid-specific, but it can also be found on somelymphoid cells.[6]
CD33 can be stimulated by any molecule withsialic acid residues such as glycoproteins or glycolipids. Upon binding, the immunoreceptor tyrosine-based inhibition motif (ITIM) of CD33, present on the cytosolic portion of the protein, is phosphorylated and acts as a docking site forSrc homology 2 (SH2) domain-containing proteins like SHP phosphatases. This results in a cascade that inhibits phagocytosis in the cell.[8]
CD33 controlsmicroglial activation but in Alzheimer disease it goes overdrive in presence of amyloid and tau proteins, its expression is known to be tied toTREM2.[9][10][11][12]
CD33 is the target ofgemtuzumab ozogamicin (trade name: Mylotarg®; Pfizer/Wyeth-Ayerst Laboratories),[13] anantibody-drug conjugate (ADC) for the treatment of patients withacute myeloid leukemia. The drug is a recombinant,humanized anti-CD33monoclonal antibody (IgG4 κ antibody hP67.6) covalently attached to the cytotoxic antitumor antibioticcalicheamicin (N-acetyl-γ-calicheamicin) via a bifunctional linker (4-(4-acetylphenoxy)butanoic acid).[14] Several mechanisms of resistance to gemtuzumab ozogamicin have been elucidated.[15] On September 1, 2017, the FDA approved Pfizer's Mylotarg.[16]
Gemtuzumab ozogamicin was initially approved by theU.S. Food and Drug Administration in 2000. However, during post marketing clinical trials researchers noticed a greater number of deaths in the group of patients who received gemtuzumab ozogamicin compared with those receiving chemotherapy alone. Based on these results,Pfizer voluntarily withdrew gemtuzumab ozogamicin from the market in mid-2010, but was reintroduced to the market in 2017.[17][18][19]
^Hernández-Caselles T, Martínez-Esparza M, Pérez-Oliva AB, Quintanilla-Cecconi AM, García-Alonso A, Alvarez-López DM, García-Peñarrubia P (January 2006). "A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: two isoforms of CD33 are generated by alternative splicing".Journal of Leukocyte Biology.79 (1):46–58.doi:10.1189/jlb.0205096.PMID16380601.S2CID21259300.
