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2821215 
Journal Article 
Optimization of chemically defined feed media for monoclonal antibody production in Chinese hamster ovary cells 
Kishishita, S; Katayama, S; Kodaira, K; Takagi, Y; Matsuda, H; Okamoto, H; Takuma, S; Hirashima, C; Aoyagi, H 
2015 
Yes 
Journal of Bioscience and Bioengineering
ISSN: 1389-1723
EISSN: 1347-4421 
120 
1 
78-84 
English 
25678240 
WOS:000356757000014 
Chinese hamster ovary (CHO) cells are the most commonly used mammalian host for large-scale commercial production of therapeutic monoclonal antibodies (mAbs). Chemically defined media are currently used for CHO cell-based mAb production. An adequate supply of nutrients, especially specific amino acids, is required for cell growth and mAb production, and chemically defined fed-batch processes that support rapid cell growth, high cell density, and high levels of mAb production is still challenging. Many studies have highlighted the benefits of various media designs, supplements, and feed addition strategies in cell cultures. In the present study, we used a strategy involving optimization of a chemically defined feed medium to improve mAb production. Amino acids that were consumed in substantial amounts during a control culture were added to the feed medium as supplements. Supplementation was controlled to minimize accumulation of waste products such as lactate and ammonia. In addition, we evaluated supplementation with tyrosine, which has poor solubility, in the form of a dipeptide or tripeptide to improve its solubility. Supplementation with serine, cysteine, and tyrosine enhanced mAb production, cell viability, and metabolic profiles. A cysteine-tyrosine-serine tripeptide showed high solubility and produced beneficial effects similar to those observed with the free amino acids and with a dipeptide in improving mAb titers and metabolic profiles. 
Amino acid; Chemically defined medium; Chinese hamster ovary cells; Monoclonal antibody; Tripeptide