Trehalose suppresses antibody aggregation during the culture of Chinese hamster ovary cells

Masayoshi Onitsuka, Miki Tatsuzawa, Ryutaro Asano, Izumi Kumagai, Akihiro Shirai, Hideaki Maseda, Takeshi Omasa

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)632-638
Number of pages7
JournalJournal of Bioscience and Bioengineering
Volume117
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Antibody aggregation
  • Antibody production
  • Bispecific diabody
  • Cell culture
  • Chemical chaperone
  • Chinese hamster ovary cell
  • Trehalose

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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