Controlling Fucosylation Levels of Antibodies with Osmolality During Cell Culture in Several Host Cell Lines
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.
KeywordsMyeloma Cell Myeloma Cell Line Perfusion Culture Viable Cell Density Medium Osmolality
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.
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