Cell Engineering and Analytical Strategies for Control of Recombinant Biopharmaceutical Aggregate Levels in Cell Culture Media

对于哺乳动物细胞在培养中产生的重组蛋白生物药物，蛋白质聚集体或寡聚体的形成可能是产品质量、有效性、免疫原性和安全性方面的严重问题。最近的研究(1，2)表明，改变培养环境可以有效地减少双特异性抗体聚集体的形成。由AZ在Gaithersburg[2]阐明的一个潜在机制被证明与补料分批培养过程中线粒体功能障碍、活性氧(ROS)积累和内质网应激导致的三肽谷胱甘肽(GSH)的代谢(氧化)受损有关。

For recombinant protein biopharmaceuticals produced by mammalian cells in culture, formation of protein aggregates or oligomers can be severe problem with respect to product quality, efficacy, immunogenicity and therefore safety. Very recent studies (1,2) show that alteration of culture environment can be an effective strategy to reduce the formation of bispecific antibody aggregates. An underlying mechanism, elucidated by AZ at Gaithersburg (2), was shown to be associated with impaired metabolism (oxidation) of the tripeptide glutathione (GSH) mediated by mitochondrial dysfunction, accumulation of reactive oxygen species (ROS) and ER stress during fed-batch culture.