| Engineering mammalian cell factories for improved recombinant monoclonal antibody production: lessons from nature? | |
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MedLine Citation:
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PMID: 15880827 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this review we consider how cell specific recombinant monoclonal antibody (Mab) production by engineered mammalian cells can be improved. Whilst it is generally recognized that Mab production is limited post-transcriptionally at folding and assembly reactions, genetic engineering strategies based on overexpression of individual chaperones or foldases in mammalian cells have not reliably increased cell specific Mab production. Given that recent studies have established that chaperones and foldases themselves exist in a large multiprotein complex, which may coordinate the sequential processing of Mabs, we propose that global expansion of all components of the secretory pathway will likely be necessary to generically improve recombinant Mab production by mammalian cells. In this context, what can be learnt from nature? Important recent studies have delineated some of the main cellular pathways involved in the differentiation of B-cells into nature's own high level Mab producers, plasma cells. This is achieved by a dramatic re-programming of cellular function where the coordinated expansion of metabolic and secretory machinery precedes Ig production, then is maintained by induction of a key intracellular signaling pathway, the unfolded protein response (UPR). Here we review genetic engineering strategies to increase cell specific production rate and discuss whether manipulation of intracellular signaling systems such as the UPR will provide a novel means to engineer mammalian cells for high level recombinant Mab production. |
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Authors:
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Diane M Dinnis; David C James |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Biotechnology and bioengineering Volume: 91 ISSN: 0006-3592 ISO Abbreviation: Biotechnol. Bioeng. Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-06-22 Completed Date: 2005-09-08 Revised Date: 2005-11-16 |
Medline Journal Info:
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Nlm Unique ID: 7502021 Medline TA: Biotechnol Bioeng Country: United States |
Other Details:
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Languages: eng Pagination: 180-9 Citation Subset: IM |
Affiliation:
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School of Engineering, University of Queensland, St. Lucia, QLD 4072, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / biosynthesis*, genetics B-Lymphocytes / metabolism* Biomimetics / methods* Gene Expression Regulation / physiology Genetic Enhancement / methods* Humans Models, Biological* Protein Engineering / methods* Recombinant Proteins / biosynthesis* Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Recombinant Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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