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An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes

Paper ID Volume ID Publish Year Pages File Format Full-Text
24831 43539 2008 7 PDF Available
Title
An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes
Abstract

The optimization of production processes for therapeutic antibodies is a continuing challenge in pharmaceutical biotechnology. Although it could be demonstrated that vector design and host cell engineering can improve transcriptional and translational efficiency and thereby result in generation of high producer cell lines, it is not clear whether introduction of transgenes that regulate protein transport or affect post-translational modifications could further improve such industrial processes.Here, we show that heterologous expression of the transcription factor X-box binding protein-1 (XBP-1) can lead to an increase in endoplasmic reticulum (ER) content and specific therapeutic antibody productivity of Chinese hamster ovary (CHO)-DG44 cells in inoculum suspension cultures. This effect translates into 40% increased overall antibody titers in a fed-batch format where cells are grown in chemically defined serum-free media. Protein-A purified antibody products from mock-transfected cells and XBP-1 transfected cells were found to be of comparable quality with regard to glycosylation pattern and physicochemical characteristics. The data demonstrate the potential of XBP-1 engineering to improve mammalian cell culture production processes to yield high amounts of a therapeutic protein product of desired quality.

Keywords
Recombinant protein production; Organelle engineering; CHO; Secretion; UPR; Endoplasmic reticulum
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An XBP-1 dependent bottle-neck in production of IgG subtype antibodies in chemically defined serum-free Chinese hamster ovary (CHO) fed-batch processes
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 135, Issue 2, 1 June 2008, Pages 217–223
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