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The pharmacological basis of anti-IgE therapy

Abstract

The treatment of asthma and allergic rhinitis using unique, humanized anti-IgE monoclonal antibodies with very particular binding specificities is now supported by the results of multiple phase II and III human clinical studies. The therapeutic efficacy of this approach is attributable to several pharmacological mechanisms. In addition to the expected effects of these monoclonal antibodies in neutralizing free IgE and inhibiting IgE production by B cells, several indirect biochemical and cellular effects have been uncovered during the course of the clinical trials. These include the accumulation of potentially beneficial IgE–anti-IgE immune complexes and the downregulation of the high-affinity IgE Fc receptors (FcɛRI) on basophils and mast cells. This article analyzes the structural basis of the specificity of the anti-IgE antibodies and pertinent results from in vitro experiments, animal model studies, and human clinical trials in an attempt to provide a cogent pharmacological interpretation of the therapeutic effects of anti-IgE therapy in both the near- and long term. The development of anti-IgE therapy over the past 10 years provides an interesting example of the emergence of a conceptually new, biotechnology-produced pharmaceutical.

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Figure 1
Figure 2: The relationship between binding sites for anti-IgE and FcɛRI or FcɛRII.
Figure 3: Probable largest stable structures of complexes formed by IgE and anti-IgE antibodies.
Figure 4: Kinetics of IgE and IgE–anti-IgE immune complexes.
Figure 5: The effect of continual anti-IgE treatment on accumulation of IgE–anti-IgE immune complexes and the downregulation of FcɛRI.

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Chang, T. The pharmacological basis of anti-IgE therapy. Nat Biotechnol 18, 157–162 (2000). https://doi.org/10.1038/72601

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