Volumen: 17 # Number : 3
Publication Date : Septiembre - Diciembre Year: 2013
Eculizumab
Authors: Brodsky AL
Abstract: Eculizumab is a chimeric monoclonal antibody -with a murine paratope and the remaining antibody molecule of human origin-
that underwent an IgG2/4 human hybridization, specifically
designed to 1) bind C5 inhibiting its activation and so to 2) block terminal complement activation, 3) avoid either immunogenicity
or inflammation, as it neither binds complement it is nor recognized by the Fc receptors of leukocytes or macrophages.
An enhanced susceptibility to N. meningitidis infections is the only immune deficiency it generates, turning a previous or concomitant vaccination a compelling issue.
Research with eculizumab has been undertaken in Paroxysmal Nocturnal Hemoglobinuria and in atypical Hemolytic Uremic Syndrome, 2 orphan diseases, with unfavorable prognosis and without a specific treatment before eculizumab was assayed. Complement mediated cell damage has, in both disorders, a chief pathogenic role. Eculizumab showed highly effective to improve the prognosis in both disorders, with a very favorable safety profile. Thus it was approved by the regulatory authorities of USA and Europe for first line treatment.
The therapeutic efficacy of eculizumab is under evaluation in other affections -typical hemolytic uremic syndrome and hemolytic
anemia due to cold agglutinins besides them-, where complement
blockade may be a promising strategy.
Key words: paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, eculizumab, humanized monoclonal
antibody, complement system
Pages : 276-284
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