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

Paper ID Volume ID Publish Year Pages File Format Full-Text
20480 43176 2014 7 PDF Available
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.

Keywords
Chinese hamster ovary cell; Cell culture; Antibody production; Antibody aggregation; Chemical chaperone; Trehalose; Bispecific diabody
First Page Preview
Trehalose suppresses antibody aggregation during the culture of Chinese hamster ovary cells
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 117, Issue 5, May 2014, Pages 632–638
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering