TY - JOUR
T1 - Trehalose suppresses antibody aggregation during the culture of Chinese hamster ovary cells
AU - Onitsuka, Masayoshi
AU - Tatsuzawa, Miki
AU - Asano, Ryutaro
AU - Kumagai, Izumi
AU - Shirai, Akihiro
AU - Maseda, Hideaki
AU - Omasa, Takeshi
N1 - Funding Information:
This study was supported by the Advanced Research for Medical Products Mining Programme of the National Institute of Biomedical Innovation (NIBIO). The authors thank Akiko Miyake (Hayashibara Co., Ltd.) for measuring the osmolality of the culture medium.
PY - 2014/5
Y1 - 2014/5
N2 - The aggregation of therapeutic antibodies during the manufacturing process is problematic because of the potential risks posed by the aggregates, such as an unexpected immune response. One of the hallmark effects of trehalose, a disaccharide consisting of two alpha-glucose units, is as a chemical chaperone with anti-aggregation activity. In this study, Chinese hamster ovary (CHO) cell line producing a diabody-type bispecific antibody were cultured in medium containing trehalose and the aggregation of the secreted proteins during the culture process was analyzed. An analysis of the various forms of the antibody (monomeric, dimeric, and large aggregates) showed that trehalose decreased the relative content of large aggregates by two thirds. The aggregation kinetics indicated that trehalose directly inhibited the polymerization and aggregation steps in a nucleation-dependent aggregation mechanism. Moreover, both specific and volumetric antibody production were increased in CHO cells cultured in trehalose-containing medium. Thus, the addition of trehalose to recombinant CHO cell cultures would offer a practical strategy for quality improvement in the production of therapeutic antibodies.
AB - The aggregation of therapeutic antibodies during the manufacturing process is problematic because of the potential risks posed by the aggregates, such as an unexpected immune response. One of the hallmark effects of trehalose, a disaccharide consisting of two alpha-glucose units, is as a chemical chaperone with anti-aggregation activity. In this study, Chinese hamster ovary (CHO) cell line producing a diabody-type bispecific antibody were cultured in medium containing trehalose and the aggregation of the secreted proteins during the culture process was analyzed. An analysis of the various forms of the antibody (monomeric, dimeric, and large aggregates) showed that trehalose decreased the relative content of large aggregates by two thirds. The aggregation kinetics indicated that trehalose directly inhibited the polymerization and aggregation steps in a nucleation-dependent aggregation mechanism. Moreover, both specific and volumetric antibody production were increased in CHO cells cultured in trehalose-containing medium. Thus, the addition of trehalose to recombinant CHO cell cultures would offer a practical strategy for quality improvement in the production of therapeutic antibodies.
KW - Antibody aggregation
KW - Antibody production
KW - Bispecific diabody
KW - Cell culture
KW - Chemical chaperone
KW - Chinese hamster ovary cell
KW - Trehalose
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U2 - 10.1016/j.jbiosc.2013.10.022
DO - 10.1016/j.jbiosc.2013.10.022
M3 - Article
C2 - 24315529
AN - SCOPUS:84897055074
VL - 117
SP - 632
EP - 638
JO - Journal of Bioscience and Bioengineering
JF - Journal of Bioscience and Bioengineering
SN - 1389-1723
IS - 5
ER -