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奥马珠单抗的奇妙历程

The Incredible Adventure of Omalizumab.

作者信息

Domingo Christian, Monserrate Daniel R, Sogo Ana, Mirapeix Rosa M

机构信息

Department of Pulmonary Medicine, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, 08202 Sabadell, Spain.

Unitat d'Anatomia, Departament de Ciències Morfològiques, Universitat Autònoma de Barcelona (UAB), 08193 Cerdanyola, Spain.

出版信息

Int J Mol Sci. 2024 Mar 6;25(5):3056. doi: 10.3390/ijms25053056.

Abstract

The basis of our current understanding of allergies begins with the discovery of IgE in the mid-1960s. The whole theory of the physiology and pathophysiology of allergic diseases, including rhinitis and asthma, dates from that period. Among the key regions of IgE identified were the FAB (fragment antigen binding) portion that has the ability to capture allergens, and the Cε3 domain, through which IgE binds to its membrane receptor. It was then postulated that blocking IgE at the level of the Cε3 domain would prevent it from binding to its receptor and thus set in motion the allergic cascade. This was the beginning of the development of omalizumab, a monoclonal antibody with an anti-IgE effect. In this article, we review the pathophysiology of allergic disease and trace the clinical development of omalizumab. We also review the benefits of omalizumab treatment that are apparently unrelated to allergies, such as its effect on immunity and bronchial remodeling.

摘要

我们目前对过敏症的理解基础始于20世纪60年代中期IgE的发现。包括鼻炎和哮喘在内的过敏性疾病的整个生理和病理生理理论都始于那个时期。在已确定的IgE关键区域中,有能够捕获过敏原的FAB(抗原结合片段)部分,以及IgE通过其与膜受体结合的Cε3结构域。当时推测,在Cε3结构域水平阻断IgE将阻止其与受体结合,从而启动过敏级联反应。这就是奥马珠单抗(一种具有抗IgE作用的单克隆抗体)研发的开端。在本文中,我们回顾了过敏性疾病的病理生理学并追溯了奥马珠单抗的临床研发过程。我们还回顾了奥马珠单抗治疗的益处,这些益处显然与过敏无关,例如其对免疫和支气管重塑的作用。

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