Controlling Fucosylation Levels of Antibodies with Osmolality During Cell Culture in Several Host Cell Lines

  • Yoshinobu Konno
  • Yuki Kobayashi
  • Ken Takahashi
  • Shinji Sakae
  • Masako Wakitani
  • Toshiyuki Suzawa
  • Keiichi Yano
  • Masamichi Koike
  • Kaori Wakamatu
  • Shinji Hosoi
Conference paper
Part of the ESACT Proceedings book series (ESACT, volume 5)

Abstract

Since a cost of therapeutic Monoclonal antibodies (MAbs) is much higher than other compounds, it is critical to produce high-efficacy MAbs efficiently. One method is to increase the effectiveness of a MAb, which in turn affects antibody-dependent cellular cytotoxicity (ADCC) is related defucosylation level (deFuc%) of MAbs. Since deFuc% of MAbs must be regulated for their quality control, it leads to careful consideration of the type of host cell employed. Thus, it is quite important to grasp the effects of culture conditions on the deFuc% in each cell line for the launched on the market and development, except for like a Chinese hamster ovary cells (CHOs) with α-1,6-fucosyltransferase gene knock out (PotelligentTM, BioWa, USA). For the MAbs produced in a rat myeloma cells (YB2/0), we found that osmolality of the culture medium is the major determinant of the deFuc%. In addition, deFuc% was not affected by the type of osmolytes (NaCl, KCl, fucose, fructose, and mannitol). We succeeded in controlling the deFuc% of MAbs arbitrarily 45–85% by maintaining medium osmolality during cultures (perfusion and fed-batch). We found the same correlation between the deFuc% and the culture osmolality in NS0 and SP2/0 cells as the in the YB2/0 cells.

Keywords

Myeloma Cell Myeloma Cell Line Perfusion Culture Viable Cell Density Medium Osmolality 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We are grateful to Drs. Mitsuo Sato, Kazuhisa Uchida, Mrs. Hiroshi Takasugi, Kazutoshi Maki, and Noriyuki Takahashi for their helpful discussions and their technical assistants.

References

  1. Tatsuya Ogawa, et al. (2001) Process for producing polypeptide (Work Ongoing 01/29246)Google Scholar
  2. Toyohide Shinkawa, et al. (2003) The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J. Biol. Chem., 278, 3466–3473Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Yoshinobu Konno
    • 1
    • 2
  • Yuki Kobayashi
    • 1
  • Ken Takahashi
    • 1
  • Shinji Sakae
    • 1
  • Masako Wakitani
    • 1
  • Toshiyuki Suzawa
    • 1
  • Keiichi Yano
    • 1
  • Masamichi Koike
    • 1
  • Kaori Wakamatu
    • 2
  • Shinji Hosoi
    • 1
  1. 1.Bio Process Research and Development LaboratoriesKyowa Hakko Kirin Co., LTD.GunmaJapan
  2. 2.Graduate School of EngineeringGunma UniversityKiryu-shiJapan

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