Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity

作者：Konno Yoshinobu^*; Kobayashi Yuki; Takahashi Ken; Takahashi Eiji; Sakae Shinji; Wakitani Masako; Yamano Kazuya; Suzawa Toshiyuki; Yano Keiichi; Ohta Toshio; Koike Masamichi; Wakamatsu Kaori; Hosoi Shinji

来源：Cytotechnology, 2012, 64(3): 249-265.

DOI：10.1007/s10616-011-9377-2

• Antibody
• Antibody-dependent cellular cytotoxicity
• Cell culture
• Fucosylation
• Glucose
• Glycosylation
• Hybridoma
• Osmolality
• YB2/0 cells

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.

• 出版日期2012-5