[Alemtuzumab: a further option for treatment of multiple sclerosis].
Alemtuzumab is a humanized monoclonal therapeutic antibody that targets the CD52 antigen which s expressed on most cells of the lymphoid lineage, exclusive of precursors. Alemtuzumab rapidly depletes CD52(+) cells from the peripheral blood. This depletion is long-lasting, and cells repopulate in a specific pattern with B cells and regulatory T cells peaking first. Alemtuzumab was examined for clinical utility in two open-labelled intervention trials in multiple sclerosis (MS). Because of very promising results its clinical efficacy was further explored in a clinical phase-II trial using s.c. interferon beta-1a as the active comparator. Severe or opportunistic infections were surprisingly rare given the long-term lymphopenia. However, up to 30% of patients developed some antibody-mediated autoimmunity. The thyroid gland was the most frequently affected organ. Immune-mediated thrombocytopenic purpura and Goodpasture's syndrome were additionally observed. This review summarizes the pre-clinical and clinical development of alemtuzumab and discusses potential modes of action as well as the pathogenetic link to the treatment emergent autoimmune phenomena.
Neurologische Klinik, Universitätsklinikum Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland. menge@uni-duesseldorf.de
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D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology*; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*
D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab