An Update on Biologic-based Therapy in Asthma
IgE is central to the pathogenesis of diseases associated with immediate hypersensitivity reactions, such as allergic asthma. IgE binds to high-affinity (FcεRI) receptors on mast cells and basophils, and to low-affinity (FcεRII) receptors on macrophages, dendritic cells and B lymphocytes. Allergens crosslink adjacent cell surface Fab components of IgE thereby activating intracellular signal transduction. This results in mast cell release of preformed mediators and synthesis and release of other mediators that contribute to bronchoconstriction and airway inflammation.
The anti-IgE biologic omalizumab (Xolair®, Genentech/Novartis), is a US FDA/EMEA-approved humanized monoclonal antibody (mAb) to the FcεRI (Cε3)-binding domain of human IgE. Early studies demonstrated inhibition of early- and late-phase allergen-induced asthmatic reactions with serum-free IgE concentrations reduced to less than 5% of baseline; omalizumab may also be able to suppress new IgE production
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