Guntern Pascal, Eggel Alexander
Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Department of BioMedical Research, University of Bern, Bern, Switzerland.
Allergy. 2020 Oct;75(10):2491-2502. doi: 10.1111/all.14308. Epub 2020 Apr 21.
About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances, scientists have started inventing strategies to block its pathophysiological activity in 1986. The initial concept of specific IgE targeting through the use of anti-IgE antibodies has gained a lot of momentum and within a few years independent research groups have reported successful generation of first murine monoclonal anti-IgE antibodies. Subsequent generation of optimized chimeric and humanized versions of these antibodies has paved the way for the development of therapeutic anti-IgE biologicals as we know them today. With omalizumab, there is currently still only one therapeutic anti-IgE antibody approved for the treatment of allergic conditions. Since its application is limited to the treatment of moderate-to-severe persistent asthma and chronic spontaneous urticaria, major efforts have been undertaken to develop alternative anti-IgE biologicals that could potentially be used in a broader spectrum of allergic diseases. Several new drug candidates have been generated and are currently assessed in pre-clinical studies or clinical trials. In this review, we highlight the molecular properties of past and present anti-IgE biologicals and suggest concepts that might improve treatment efficacy of future drug candidates.
在免疫球蛋白E（IgE）被鉴定及其在针对通常无害物质的过敏性超敏反应中的关键作用被发现约20年后，科学家们于1986年开始研发阻断其病理生理活性的策略。通过使用抗IgE抗体靶向特异性IgE的最初概念获得了很大的发展动力，并且在几年内，独立的研究小组报告成功制备了首批鼠源单克隆抗IgE抗体。随后对这些抗体进行优化，生成嵌合和人源化版本，为如今我们所知的治疗性抗IgE生物制剂的开发铺平了道路。目前，仅有奥马珠单抗这一种治疗性抗IgE抗体被批准用于治疗过敏性疾病。由于其应用仅限于治疗中重度持续性哮喘和慢性自发性荨麻疹，因此人们付出了巨大努力来开发可能用于更广泛过敏性疾病的替代性抗IgE生物制剂。已经产生了几种新的候选药物，目前正在进行临床前研究或临床试验评估。在本综述中，我们重点介绍了过去和现在的抗IgE生物制剂的分子特性，并提出了可能提高未来候选药物治疗效果的概念。
