Gyorgypal Aron, Chaturvedi Antash, Chopda Viki, Zhang Haoran, Chundawat Shishir P S
Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 USA.
Cytotechnology. 2025 Feb;77(1):40. doi: 10.1007/s10616-024-00690-7. Epub 2025 Jan 9.
The choice of media and feeds significantly influences the performance of Chinese Hamster Ovary (CHO) mammalian cell cultures in producing desired biologics like monoclonal antibodies (mAb). Sub-optimal nutrient feed/media composition can severely impact cell proliferation and the quality of the final mAb product. For instance, proper protein glycosylation, crucial for mAb stability, safety, and efficacy, heavily relies on cell culture conditions. Currently, starter CHO culture media and daily supplemental feeds used in industrial manufacturing consist of proprietary composition of nutrients critical for mAb production. Standardized optimal media/feed combinations necessary for different cell lines are often lacking, necessitating individualized optimization for each cell line and mAb product. Here, we focused on a CHO-K1 cell line engineered to produce a Trastuzumab biosimilar and evaluated the effects of fourteen commercially relevant basal media and seven feeds on cell culture parameters such as viable cell density, viability, nutrient consumption, metabolite production, mAb titer, and mAb N-glycosylation. Our findings demonstrate clearly that the compositions of the basal medium and feed play a pivotal role in enhancing cell growth and mAb production. This work offers valuable insights into strategies for optimizing feed/media composition for glycosylated monoclonal antibody production using CHO cells.
The online version contains supplementary material available at 10.1007/s10616-024-00690-7.
培养基和补料的选择对中国仓鼠卵巢(CHO)哺乳动物细胞培养生产单克隆抗体(mAb)等所需生物制品的性能有显著影响。次优的营养补料/培养基组成会严重影响细胞增殖和最终mAb产品的质量。例如,对mAb的稳定性、安全性和功效至关重要的蛋白质糖基化很大程度上依赖于细胞培养条件。目前,工业生产中使用的起始CHO培养基和每日补充补料由对mAb生产至关重要的营养成分的专有组成构成。不同细胞系所需的标准化最佳培养基/补料组合往往缺乏,因此需要针对每个细胞系和mAb产品进行个性化优化。在此,我们聚焦于一种经工程改造以生产曲妥珠单抗生物类似药的CHO-K1细胞系,并评估了十四种商业相关基础培养基和七种补料对细胞培养参数的影响,如活细胞密度、活力、营养物质消耗、代谢产物生成、mAb滴度和mAb N-糖基化。我们的研究结果清楚地表明,基础培养基和补料的组成在促进细胞生长和mAb生产中起着关键作用。这项工作为优化使用CHO细胞生产糖基化单克隆抗体的补料/培养基组成策略提供了有价值的见解。
在线版本包含可在10.1007/s10616-024-00690-7获取的补充材料。