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Identification of cell culture conditions to control protein aggregation of IgG fusion proteins expressed in Chinese hamster ovary cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
34679 45039 2012 7 PDF Available
Title
Identification of cell culture conditions to control protein aggregation of IgG fusion proteins expressed in Chinese hamster ovary cells
Abstract

The presence of aggregated forms of proteins can be problematic for therapeutics due to the potential for immunogenic and pharmacokinetic issues. Although downstream processing can remove the aggregated forms, inhibiting aggregate formation upstream during the cell culture stage could reduce the burden on downstream processing and potentially improve process yields. This study first examined the effects of environmental factors (temperature, pH, and dissolved oxygen) and medium components (bivalent copper ion, cysteine, and cystine) on the aggregation of two different recombinant fusion proteins expressed by Chinese hamster ovary (CHO) cells. Any strategy to reduce protein aggregation upstream during cell culture must also consider potential effects on critical upstream parameters such as cell growth, harvest titer, and protein sialylation levels. Manipulating the culture temperature shift and cystine concentration in the medium were both identified as effective and practical strategies for reducing protein aggregation in both CHO-cell expression systems. Furthermore, a combination of both strategies was more effective in reducing protein aggregation levels compared to either approach individually; and without any negative effects on harvest titer and protein sialylation. This study demonstrates a practical methodology for decreasing protein aggregation during upstream processing and emphasizes the importance of process understanding to ensure production of recombinant glycoprotein therapeutics with consistent product quality.

► Studied environmental and CHO culture additives for effects on protein aggregation. ► Culture temperature shift and cystine concentration were effective in reducing aggregation. ► Both approaches minimally affected cell growth, protein titer, and sialylation. ► Use of both approaches together provided improved capability to limit aggregation. ► Confirmed using two different recombinant proteins, both in CHO cells.

Keywords
Protein aggregation; IgG fusion protein; Cell culture conditions; CHO; Mammalian cell culture
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Identification of cell culture conditions to control protein aggregation of IgG fusion proteins expressed in Chinese hamster ovary cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 47, Issue 1, January 2012, Pages 69–75
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us