IgG 样双特异性抗体纯化的一般策略。

IF 2.5 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Yifeng Li
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引用次数: 0

摘要

双特异性抗体(bsAbs)可同时结合两种不同的抗原或表位。与传统的单特异性 mAbs 相比,双特异性抗体具有双重靶向能力,可实现新的作用机制,从而获得治疗优势。近年来,bsAbs 的数量迅速增长,开发中的 bsAbs 形式多样。其中,以含 Fc 的 IgG 样 bsAbs 为主,它们可以以非对称或对称的形式构建。对于非对称形式的 bsAbs,其组装需要多条不同的链,尽管已开发出许多策略来促进所需的链配对,但与产品相关的变体,如游离链、半分子和配对错误的物种通常会在不同程度上存在。对于对称性抗体,聚集体和截断变体的增加往往与抗体的生产有关。一般来说,与普通 mAbs 相比,bsAbs 给下游团队带来了更大的挑战。在过去几年中,我们的团队成功开发了 30 多种不同格式的 70 多种 bsAbs 的下游工艺,积累了丰富的经验。本综述将介绍我们在纯化这些具有挑战性的分子时所采用的一般策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
General strategies for IgG-like bispecific antibody purification.

Bispecific antibodies (bsAbs) can simultaneously bind two different antigens or epitopes. Their dual-targeting capability enables novel mechanisms of action, gaining therapeutic advantages over conventional monospecific mAbs. In recent years, the number of bsAbs grows rapidly and bsAbs under development are available in diverse formats. In particular, Fc-containing IgG-like bsAbs, which represent the major group, can be constructed in asymmetric or symmetric format. For asymmetric ones, whose assembly requires multiple distinct chains, although numerous strategies have been developed to promote desired chain pairing, product-related variants such as free chains, half molecules and mispaired species are usually present at various levels. For symmetric ones, increased level of aggregates and truncating variants is often associated with their production. In general, bsAbs pose greater challenges to the downstream team than regular mAbs. In the past few years, our team successfully developed the downstream process for over 70 bsAbs in greater than 30 different formats and accumulated substantial experience. This review introduces general strategies that we have used while purifying these challenging molecules.

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来源期刊
Biotechnology Progress
Biotechnology Progress 工程技术-生物工程与应用微生物
CiteScore
6.50
自引率
3.40%
发文量
83
审稿时长
4 months
期刊介绍: Biotechnology Progress , an official, bimonthly publication of the American Institute of Chemical Engineers and its technological community, the Society for Biological Engineering, features peer-reviewed research articles, reviews, and descriptions of emerging techniques for the development and design of new processes, products, and devices for the biotechnology, biopharmaceutical and bioprocess industries. Widespread interest includes application of biological and engineering principles in fields such as applied cellular physiology and metabolic engineering, biocatalysis and bioreactor design, bioseparations and downstream processing, cell culture and tissue engineering, biosensors and process control, bioinformatics and systems biology, biomaterials and artificial organs, stem cell biology and genetics, and plant biology and food science. Manuscripts concerning the design of related processes, products, or devices are also encouraged. Four types of manuscripts are printed in the Journal: Research Papers, Topical or Review Papers, Letters to the Editor, and R & D Notes.
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