title: The enhancement of antibody concentration and achievement of high cell density CHO cell cultivation by adding nucleoside.
abstract: Recently, with the dramatic increase in demand for therapeutic antibodies, Chinese hamster ovary (CHO) cell culture systems have made significant progress in recombinant antibody production. Over the past two decades, recombinant antibody productivity has been improved by more than 100-fold. Medium optimization has been identified as an important key approach for increasing product concentrations. In this study, we evaluated the effects of deoxyuridine addition to fed-batch cultures of antibody-expressing CHO cell lines. Furthermore, we investigated the effects of combined addition of deoxyuridine, thymidine, and deoxycytidine. Our results suggest that addition of these pyrimidine nucleosides can increase CHO cell growth, with no significant change in the specific production rate. As a result of the increased cell growth, the antibody concentration was elevated and we were able to achieve more than 9 g/L during 16 days of culture. Similar effects of nucleoside addition were observed in fed-batch cultures of a Fab fragment-expressing CHO cell line, and the final Fab fragment concentration was more than 4 g/L. This nucleoside addition strategy could be a powerful platform for efficient antibody production.
authors.affiliation: Institute of Bioscience and Bioindustry, Tokushima University, 2-1 Minamijosanjima-cho, Tokushima, 770-8506, Japan.|Biotechnology Laboratories, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba, Ibaraki, 300-2698, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Biotechnology Laboratories, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba, Ibaraki, 300-2698, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Biotechnology Laboratories, Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba, Ibaraki, 300-2698, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Wada
authors.affiliation: Institute of Bioscience and Bioindustry, Tokushima University, 2-1 Minamijosanjima-cho, Tokushima, 770-8506, Japan. omasa@bio.eng.osaka-u.ac.jp.|Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. omasa@bio.eng.osaka-u.ac.jp.
authors.forename: Takeshi
authors.identifier: http://orcid.org/0000-0003-0635-3862
authors.initials: T
authors.lastname: Omasa
keywords: Cell culture medium; Chinese hamster ovary (CHO) cell; Nucleoside; Therapeutic antibody