title: Trehalose suppresses antibody aggregation during the culture of Chinese hamster ovary cells.
abstract: 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.
authors: Institute of Technology and Science, The University of Tokushima, Minamijosanjima-cho 2-1, Tokushima 770-8506, Japan. Electronic address: onitsuka@bio.tokushima-u.ac.jp.
authors: Masayoshi
authors: M
authors: Onitsuka
authors: Advanced Technology and Science, The University of Tokushima, Minamijosanjima-cho 2-1, Tokushima 770-8506, Japan.
authors: Miki
authors: M
authors: Tatsuzawa
authors: Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11-606 Aoba-yama, Aramaki, Aoba-ku, Sendai 980-8579, Japan.
authors: Ryutaro
authors: R
authors: Asano
authors: Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11-606 Aoba-yama, Aramaki, Aoba-ku, Sendai 980-8579, Japan.
authors: Izumi
authors: I
authors: Kumagai
authors: Institute of Technology and Science, The University of Tokushima, Minamijosanjima-cho 2-1, Tokushima 770-8506, Japan.
authors: Akihiro
authors: A
authors: Shirai
authors: Institute of Technology and Science, The University of Tokushima, Minamijosanjima-cho 2-1, Tokushima 770-8506, Japan.
authors: Hideaki
authors: H
authors: Maseda
authors: Institute of Technology and Science, The University of Tokushima, Minamijosanjima-cho 2-1, Tokushima 770-8506, Japan; Department of Biotechnology, Graduate School of Engineering, Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan.
authors: Takeshi
authors: T
authors: Omasa
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D019149:Bioreactors; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D011485:Protein Binding / Q000187:drug effects; D014199:Trehalose / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018033:Antibodies, Bispecific; D003470:Culture Media; D014199:Trehalose
keywords: Antibody aggregation; Antibody production; Bispecific diabody; Cell culture; Chemical chaperone; Chinese hamster ovary cell; Trehalose