title: Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity.
abstract: Antibody-dependent cellular cytotoxicity (ADCC) is dependent on the fucose content of oligosaccharides bound to monoclonal antibodies (MAbs). As MAbs with a low fucose content exhibit high ADCC activity, it is important to control the defucosylation levels (deFuc%) of MAbs and to analyze the factors that affect deFuc%. In this study, we observed that the deFuc% was inversely related to culture medium osmolality for MAbs produced in the rat hybridoma cell line YB2/0, with r                         (2) values as high as 0.92. Moreover, deFuc% exhibited the same correlation irrespective of the type of compound used for regulating osmolality (NaCl, KCl, fucose, fructose, creatine, or mannitol) at a culture scale ranging from 1 to 400 L. We succeeded in controlling MAb deFuc% by maintaining a constant medium osmolality in both perfusion and fed-batch cultures. In agreement with these observations, reverse transcription PCR analyses revealed decreased transcription of genes involved in glycolysis, GDP-fucose supply, and fucose transfer under hypoosmotic conditions.
authors.affiliation: Bio Process Research and Development Laboratories, Kyowa Hakko Kirin Co., Ltd., 100-1 Hagiwara-machi, Takasaki-shi, Gunma, 370-0013, Japan, yoshinobu.konno@kyowa-kirin.co.jp.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Konno
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Ken
authors.initials: K
authors.lastname: Takahashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Takahashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakae
authors.forename: Masako
authors.initials: M
authors.lastname: Wakitani
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Suzawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yano
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohta
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koike
authors.forename: Kaori
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Hosoi