Accession Number : AD1047226

Title :   Novel IgE Inhibitors for the Treatment of Food Allergies

Descriptive Note : Technical Report,30 Sep 2015,29 Sep 2016

Corporate Author : Stanford University School of Medicine Stanford United States

Personal Author(s) : Jardetzky, Theodore

Full Text :

Report Date : 01 Oct 2016

Pagination or Media Count : 13

Abstract : Omalizumab is currently the only FDA approved monoclonal anti-IgE therapy. We solved the IgE:omalizumab crystal structure to 2.54 . This structure elucidates the mechanism of omalizumab inhibition of IgE:FcRI and IgE:CD23 interactions, and explains omalizumabs selectivity for free circulating IgE. Surprisingly, the complex structure shares significant similarity with the disruptive IgE inhibitor E2_79, and provides mechanistic insight into the efficiency with which disruptive inhibitors are able to bind to, and accelerate FcRI dissociation from preformed IgE:FcRI complexes. Structural information from the IgE:omalizumab complex was used to generate a point mutation in the IgE-Fc, yielding an omalizumab-resistant IgE. Omalizumab-resistant IgE, in combination with omalizumab, promotes the exchange of the IgE repertoire on human basophils. This combination treatment demonstrates the possibility of substituting rather than depleting the IgE repertoire, thereby exchanging harmful, allergen-specific IgE while maintaining endogenous IgE-dependent regulatory mechanisms that may further suppress the allergic response.

Descriptors :   ALLERGY AND IMMUNOLOGY , antibodies , inhibitors

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE