Institute of Biochemical Engineering, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
CEQIATEC, Costa Rica Institute of Technology (TEC), Cartago, Costa Rica.
AMB Express. 2016 Dec;6(1):48. doi: 10.1186/s13568-016-0221-0. Epub 2016 Jul 22.
Market demands for monoclonal antibodies (mAbs) are steadily increasing worldwide. As a result, production processes using Chinese hamster ovary cells (CHO) are in the focus of ongoing intensification studies for maximizing cell-specific and volumetric productivities. This includes the optimization of animal-derived component free (ADCF) cultivation media as part of good cell culture practice. Dipeptides are known to improve CHO culture performance. However, little or even conflicting assumptions exist about their putative import and functionality inside the cells. A set of well-known performance boosters and new dipeptide prospects was evaluated. The present study revealed that dipeptides are indeed imported in the cells, where they are decomposed to the amino acids building blocks. Subsequently, they are metabolized or, unexpectedly, secreted to the medium. Monoclonal antibody production boosting additives like L-alanine-L-glutamine (AQ) or glycyl-L-glutamine (GQ) can be assigned to fast or slow dipeptide uptake, respectively, thus pinpointing to the need to study dipeptide kinetics and to adjust their feeding individually for optimizing mAb production.
全球对单克隆抗体（mAbs）的市场需求正在稳步增长。因此，使用中国仓鼠卵巢细胞（CHO）的生产工艺正在进行持续的强化研究，以最大限度地提高细胞特异性和体积产率。这包括优化无动物源性成分（ADCF）培养介质，这是良好细胞培养实践的一部分。二肽已知可提高 CHO 培养性能。然而，关于它们在细胞内的潜在导入和功能，存在着很少甚至相互矛盾的假设。一组知名的性能增强剂和新的二肽前景被评估。本研究表明，二肽确实被细胞吸收，在细胞内被分解为氨基酸构建块。随后，它们被代谢或出人意料地分泌到培养基中。单克隆抗体生产促进添加剂，如 L-丙氨酸-L-谷氨酰胺（AQ）或甘氨酰-L-谷氨酰胺（GQ），可以分别被分配为快速或慢速二肽摄取，从而指出需要研究二肽动力学，并单独调整它们的喂养以优化 mAb 生产。
