Ha Tae Kwang, Kim Dongil, Kim Che Lin, Grav Lise Marie, Lee Gyun Min
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby 2800, Denmark.
Department of Biological Sciences, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
Biotechnol Adv. 2022 Jan-Feb;54:107831. doi: 10.1016/j.biotechadv.2021.107831. Epub 2021 Sep 2.
Chinese hamster ovary (CHO) cells are the most widely used mammalian host cells for the commercial production of therapeutic proteins. Fed-batch culture is widely used to produce therapeutic proteins, including monoclonal antibodies, because of its operational simplicity and high product titer. Despite technical advances in the development of culture media and cell cultures, it is still challenging to maintain high productivity in fed-batch cultures while also ensuring good product quality. In this review, factors that affect the quality attributes of therapeutic proteins in recombinant CHO (rCHO) cell culture, such as glycosylation, charge variation, aggregation, and degradation, are summarized and categorized into three groups: culture environments, chemical additives, and host cell proteins accumulated in culture supernatants. Understanding the factors that influence the therapeutic protein quality in rCHO cell culture will facilitate the development of large-scale, high-yield fed-batch culture processes for the production of high-quality therapeutic proteins.
中国仓鼠卵巢（CHO）细胞是用于商业生产治疗性蛋白质的最广泛使用的哺乳动物宿主细胞。由于其操作简单和产品滴度高，补料分批培养被广泛用于生产治疗性蛋白质，包括单克隆抗体。尽管在培养基和细胞培养的开发方面取得了技术进步，但在补料分批培养中保持高生产率同时确保良好的产品质量仍然具有挑战性。在这篇综述中，总结了影响重组CHO（rCHO）细胞培养中治疗性蛋白质质量属性的因素，如糖基化、电荷变异、聚集和降解，并将其分为三类：培养环境、化学添加剂和培养上清液中积累的宿主细胞蛋白。了解影响rCHO细胞培养中治疗性蛋白质质量的因素将有助于开发大规模、高产的补料分批培养工艺，以生产高质量的治疗性蛋白质。
