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[治疗性抗体及相关产品:选择正确的结构以取得成功]

[Therapeutic antibodies and related products: choosing the right structure for success].

作者信息

Beck Alain, Wagner-Rousset Elsa, Wurch Thierry, Corvaia Nathalie

机构信息

Centre d'immunologie Pierre Fabre (www.cipf.com), 5, avenue Napoléon III, 74160 Saint-Julien-en-Genevois, France.

出版信息

Med Sci (Paris). 2009 Dec;25(12):1024-32. doi: 10.1051/medsci/200925121024.

Abstract

Monoclonal antibodies (mAb) and related-products represent the fastest growing class of therapeutics in the biotechnological and pharmaceutical industry. In just as short as 20 years, more than 30 immunoglobulins (IgG) and derivatives have been approved in a wide range of indications (oncology, inflammation and auto-immunity, transplantation, angioplasty, hematology, ophthalmology, viral infections, allergy). The mAb structure toolbox contains mouse, chimeric, humanized and human antibodies from different isotypes (IgG1, 2 and 4), as well as IgG-related products (immunoconjugates, radio-immunoconjugates, Fab fragments, Fc-fusion proteins and peptides, bispecifics). Furthermore from a structural point of view, mAb glycosylation is linked to their production systems and may impact on their effector functions and immunogenicity. Based on the current knowledge, choosing the right antibody format, isotype and glycosylation profile are some of the key issues to address early during the lead selection.

摘要

单克隆抗体(mAb)及其相关产品是生物技术和制药行业中增长最快的一类治疗药物。在短短20年时间里,已有30多种免疫球蛋白(IgG)及其衍生物在广泛的适应症(肿瘤学、炎症与自身免疫、移植、血管成形术、血液学、眼科、病毒感染、过敏)中获得批准。单克隆抗体结构工具箱包含来自不同亚型(IgG1、2和4)的小鼠、嵌合、人源化和人抗体,以及IgG相关产品(免疫偶联物、放射免疫偶联物、Fab片段、Fc融合蛋白和肽、双特异性抗体)。此外,从结构角度来看,单克隆抗体的糖基化与它们的生产系统相关联,并且可能影响其效应功能和免疫原性。基于目前的知识,选择合适的抗体形式、亚型和糖基化谱是在先导化合物筛选早期需要解决的一些关键问题。

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