Recombinant antibodies aggregation and overcoming strategies in CHO cells

Abstract

Mammalian cell lines are frequently used as the preferred host cells for producing recombinant therapeutic proteins (RTPs) having post-translational modified modifications similar to those observed in proteins produced by human cells. Nowadays, most RTPs approved for marketing are produced in Chinese hamster ovary (CHO) cells. Recombinant therapeutic antibodies (RTAs) are among the most important and promising RTPs for biomedical applications. A major limitation associated with the use of RTAs is their aggregation, which can be caused by a variety of factors; this results in a reduction of quality. RTA aggregations are especially concerning as they can trigger human immune responses in humans and may be fatal. Therefore, the mechanisms underlying RTA aggregation and measures for avoiding aggregation are interesting topics in RTAs research. In this review, we discuss recent progress in the field of RTAs aggregation, with a focus on factors that cause aggregation during RTA production and the development of strategies for overcoming RTA aggregation. KEY POINTS: • The recombinant antibody aggregation in mammalian cell systems is reviewed. • Intracellular environment and extracellular parameters influence recombinant antibody aggregation. • Reducing the aggregations can improve the quality of recombinant antibodies.

Keywords: Aggregation; Bioprocess engineering; Chinese hamster ovary cells; Folding; Recombinant antibody.