The pharmacological basis of anti-IgE therapy

被引:224
作者
Chang, TW [1 ]
机构
[1] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu, Taiwan
关键词
immunoglobulin E; anti-IgE; allergy; asthma; humanized antibodies; Fc epsilon RI; immune complexes;
D O I
10.1038/72601
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 (Fc epsilon RI) 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.
引用
收藏
页码:157 / 162
页数:6
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