Advances in recombinant antibody manufacturing.

Advances in recombinant antibody manufacturing.
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重组抗体制造的进展。

DOI:
10.1007/s00253-016-7388-9
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发表时间:
2016-04
影响因子:
5
通讯作者:
Reinhart D
Reinhart D
中科院分区:
工程技术2区
文献类型:
--
作者:
Kunert R;Reinhart D

文献摘要

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自从中国仓鼠卵巢(CHO)细胞首次用于重组蛋白表达以来,通过大量的进展,生产工艺得到了稳步改进。在这篇综述中,我们重点介绍了几个关键的里程碑,从CHO细胞开始用于表达单抗(MAb)到今天,这些里程碑都有助于CHO细胞的成功。影响生产过程产量的主要因素是积累所需生物量的时间、过程持续时间和比生产率。通过比较不同表达系统的最大细胞密度和比生长速率,强调了不同细胞系统的限制参数,全面阐述了改良宿主细胞系的科学途径和技术。除了对现有系统的定量评估外,还分析了宿主细胞系的质量决定特性,即翻译后修饰,并与自然产生的人血浆中的多克隆免疫球蛋白组分进行了比较。综上所述,有许多不同的单抗表达系统可用,也正在进行科学研究。然而,CHO细胞是最频繁被研究的细胞系,直到今天仍然是生产单抗的主力。
Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.