Expression of recombinant antibodies.

Expression of recombinant antibodies.
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DOI:
10.3389/fimmu.2013.00217
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发表时间:
2013
影响因子:
7.3
通讯作者:
Schirrmann T
Schirrmann T
中科院分区:
医学2区
文献类型:
--
作者:
Frenzel A;Hust M;Schirrmann T

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重组抗体在研究和诊断中是高度特异性的检测探针,并且在过去二十年中已成为增长最快的一类治疗性蛋白质。通过体外选择系统,特别是噬菌体展示,抗体的产生已大大加速。已经开发出越来越多种类的重组生产系统,从革兰氏阴性菌和阳性菌、酵母和丝状真菌、昆虫细胞系、哺乳动物细胞到转基因植物和动物。目前,几乎所有治疗性抗体仍然在哺乳动物细胞系中生产,以降低由于改变的非人类糖基化模式而产生的免疫原性风险。然而,糖基化工程酵母、昆虫细胞系和转基因植物的最新进展有望获得具有“类人”翻译后修饰的抗体。此外,包括无糖基化的双特异性抗体在内的较小抗体片段已在细菌中成功生产,并已进入临床试验阶段。预计在未来几年内将出现首批来自非哺乳动物来源的治疗性抗体产品。在这篇综述中,我们重点关注当前的抗体生产系统,包括它们在不同应用中的适用性。
Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.
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