International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453002, Henan, China.
Appl Microbiol Biotechnol. 2022 Jun;106(11):3913-3922. doi: 10.1007/s00253-022-11977-0. Epub 2022 May 24.
Mammalian cell lines are frequently used as the preferred host cells for producing recombinant therapeutic proteins (RTPs) having post-translational modified modifications similar to those observed in proteins produced by human cells. Nowadays, most RTPs approved for marketing are produced in Chinese hamster ovary (CHO) cells. Recombinant therapeutic antibodies (RTAs) are among the most important and promising RTPs for biomedical applications. A major limitation associated with the use of RTAs is their aggregation, which can be caused by a variety of factors; this results in a reduction of quality. RTA aggregations are especially concerning as they can trigger human immune responses in humans and may be fatal. Therefore, the mechanisms underlying RTA aggregation and measures for avoiding aggregation are interesting topics in RTAs research. In this review, we discuss recent progress in the field of RTAs aggregation, with a focus on factors that cause aggregation during RTA production and the development of strategies for overcoming RTA aggregation. KEY POINTS: • The recombinant antibody aggregation in mammalian cell systems is reviewed. • Intracellular environment and extracellular parameters influence recombinant antibody aggregation. • Reducing the aggregations can improve the quality of recombinant antibodies.
哺乳动物细胞系常被用作生产具有类似人细胞产生的蛋白质的翻译后修饰的重组治疗性蛋白(RTP)的首选宿主细胞。如今,大多数获得批准上市的 RTP 都是在中华仓鼠卵巢(CHO)细胞中生产的。重组治疗性抗体(RTA)是生物医学应用中最重要和最有前途的 RTP 之一。与使用 RTA 相关的一个主要限制是它们的聚集,这可能是由多种因素引起的;这会导致质量下降。RTA 聚集尤其令人担忧,因为它们可能在人类中引发人类免疫反应,并且可能是致命的。因此,RTA 聚集的机制以及避免聚集的措施是 RTA 研究中的有趣课题。在这篇综述中,我们讨论了 RTA 聚集领域的最新进展,重点讨论了在 RTA 生产过程中导致聚集的因素以及克服 RTA 聚集的策略的发展。要点:
• 综述了哺乳动物细胞系统中重组抗体的聚集。
• 细胞内环境和细胞外参数影响重组抗体的聚集。
• 减少聚集可以提高重组抗体的质量。