title: Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production.
abstract: Elevated serum levels of both total and allergen-specific immunoglobulin E (IgE) correlate with atopic diseases such as allergic rhinitis and allergic asthma. Neutralization of IgE by anti-IgE antibodies can effectively treat allergic asthma. Preclinical studies indicate that targeting membrane IgE-positive cells with antibodies against M1 prime can inhibit the production of new IgE and significantly reduce the levels of serum IgE. We report results from two trials that investigated the safety, pharmacokinetics, and activity of quilizumab, a humanized monoclonal antibody targeting specifically the M1 prime epitope of membrane IgE, in subjects with allergic rhinitis (NCT01160861) or mild allergic asthma (NCT01196039). In both studies, quilizumab treatment was well tolerated and led to reductions in total and allergen-specific serum IgE that lasted for at least 6 months after the cessation of dosing. In subjects with allergic asthma who were subjected to an allergen challenge, quilizumab treatment blocked the generation of new IgE, reduced allergen-induced early and late asthmatic airway responses by 26 and 36%, respectively, and reduced allergen-induced increases in sputum eosinophils by ~50% compared with placebo. These studies indicate that targeting of membrane IgE-expressing cells with anti-M1 prime antibodies can prevent IgE production in humans.
authors.affiliation: McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA. harris.jeffrey@gene.com.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Harris
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec G1V 4G5, Canada.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Heleen
authors.initials: H
authors.lastname: Scheerens
authors.affiliation: University of British Columbia, Vancouver, British Columbia V5Z 1M9, Canada.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Fitzgerald
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Putnam
authors.affiliation: University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8, Canada.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Cockcroft
authors.affiliation: University of Saskatchewan, Saskatoon, Saskatchewan S7N 0W8, Canada.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Davis
authors.affiliation: University of Calgary, Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Leigh
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Karolinska University Hospital, Stockholm S-141 86, Sweden.
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Yehong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Romeo
authors.initials: R
authors.lastname: Maciuca
authors.affiliation: University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Irvin
authors.initials: I
authors.lastname: Mayers
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: X Charlene
authors.initials: XC
authors.lastname: Liao
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: Lawren C
authors.initials: LC
authors.lastname: Wu
authors.affiliation: Genentech Inc., South San Francisco, CA 94080, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Matthews
authors.affiliation: McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000939:Epitopes; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D007073:Immunoglobulin E