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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.

journal_name

Sci Transl Med

journal_title

Science translational medicine

authors

Gauvreau GM,Harris JM,Boulet LP,Scheerens H,Fitzgerald JM,Putnam WS,Cockcroft DW,Davis BE,Leigh R,Zheng Y,Dahlén B,Wang Y,Maciuca R,Mayers I,Liao XC,Wu LC,Matthews JG,O'Byrne PM

doi

10.1126/scitranslmed.3008961

subject

Has Abstract

pub_date

2014-07-02 00:00:00

pages

243ra85

issue

243

eissn

1946-6234

issn

1946-6242

pii

6/243/243ra85

journal_volume

6

pub_type

杂志文章,多中心研究,随机对照试验

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