Quilizumab is an Afucosylated Humanized Anti-M1 Prime Therapeutic Antibody
Clinical Anti-Inflammatory & Anti-Allergy Drugs,
Hans D. Brightbill, Yuwen L. Lin, Zhonghua Lin, Martha Tan, Y. Gloria Meng, Mercedesz Balazs, Shan Chung and Lawren C. WuAffiliation:
Department of Immunology, Genentech Inc., 1 DNA Way, MS 34, South San Francisco, CA 94080, USA.
AbstractDepletion of IgE-switched B cells may be an efficacious therapy for the treatment of allergic asthma. A humanized monoclonal IgG1 antibody against the M1 prime segment of human membrane IgE on IgE-switched B cells can reduce serum IgE by depleting IgE-producing cells. Here we report that removal of the core fucose in the Fc glycan of this anti-M1 prime antibody increases its binding affinity for human FcγRIII receptors compared to the wildtype antibody. The enhancement in binding to FcγRIII results in increased antibody potency for the in vitro depletion of IgE-positive cells in antibody-dependent cell-mediated cytotoxicity assays and for the in vivo reduction of serum IgE in mice reconstituted with human immune cells. This afucosylated anti-M1 prime antibody is known as quilizumab and is in clinical development for the treatment of allergic asthma.
ADCC, afucosylation, asthma, IgE, quilizumab.
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