CD52 antigen, a 12-amino acid glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein of unknown function. CD52 is highly expressed on both normal and malignant lymphocytes (B and T cells) and is also found on monocytes, macrophages and eosinophils, in addition to the male reproductive tract. Radioisotopic studies have estimated that approximately 5% of lymphocyte cell surfaces are covered by CD52 molecules. Importantly, because CD52 antigen is not expressed on CD34+ hematopoietic progenitor cells, alemtuzumab does not interfere with early hematopoietic progenitor cell development. To date, the most effective CD52 targeted therapy has been alemtuzumab, a humanized monoclonal antibody genetically engineered by grafting rat complementarity determining regions (CDRs) onto human framework regions fused to human IgG1 that binds to an epitope overlapping the C-terminal part of the CD52 peptide along with part of the GPI anchor. Whilst the mechanism of in vivo cell killing is unclear, in vitro studies have revealed that upon binding to the cell surface CD52, alemtuzumab induces cell destruction via activation of complement dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC); however studies in human CD52 transgenic mice have confirmed the importance of ADCC in vivo, but suggest that CDC may not be involved. In addition, intracellular signal transduction by ligation of CD52 leading to caspase-8 dependent and independent apoptosis has also been identified as a potential mechanism of cytolytic action by alemtuzumab
Gribben J G, Hallek M. Rediscovering alemtuzumab: current and emerging therapeutic roles[J]. British journal of haematology, 2009, 144(6): 818-831.
Holgate RGE, Weldon R, Jones TD, Baker MP. Characterisation of a Novel Anti-CD52 Antibody with Improved Efficacy and Reduced Immunogenicity. Chatenoud L, ed. PLoS ONE. 2015;10(9):e0138123.