| Covalent dimerization of camelidae anti-human TNF-alpha single domain antibodies by the constant kappa light chain domain improves neutralizing activity. | |
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MedLine Citation:
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PMID: 20047190 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The tumor necrosis factor-alpha (TNFalpha) plays an important role in a number of chronic inflammatory disorders. Monoclonal camelidae variable heavy chain domain-only antibodies (V(H)H) have been developed to antagonize the action of human TNFalpha (anti-TNF-V(H)H). Here we describe a strategy to obtain functional dimeric anti-TNF-V(H)H molecules, based on the C-terminal fusion of a kappa light chain domain to the anti-TNF-V(H)H. The resulting fusion protein was transiently expressed by use of viral vectors in Nicotiana benthamiana((Nb)) leaves and purified. Competitive ELISA and cell cytotoxicity assays revealed that the dimerized anti-(Nb)TNF-V(H)H(Ckappa) proteins blocked TNFalpha-activity more effectively than either the monomeric Escherichia coli((Ec)) produced anti-(Ec)TNF-V(H)H or the monomeric anti-(Nb)TNF-V(H)H(Ckappa). We suggest that enhanced inhibition shown by dimeric anti-(Nb)TNF-V(H)H(Ckappa) proteins is achieved by an increase in avidity. |
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Authors:
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Martin Giersberg; Doreen M Floss; Sergey Kipriyanov; Udo Conrad; J?rgen Scheller |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biotechnology and bioengineering Volume: 106 ISSN: 1097-0290 ISO Abbreviation: Biotechnol. Bioeng. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-03-29 Completed Date: 2010-06-07 Revised Date: - |
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: 161-6 Citation Subset: IM |
Affiliation:
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Institute of Plant Genetics and Crop Plant Research (IPK), Phytoantibodies, D-06466 Gatersleben, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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genetics,
pharmacology* Antibodies, Neutralizing / genetics, pharmacology* Dimerization Gene Expression Genetic Vectors Humans Immunoglobulin Light Chains / genetics, pharmacology* Immunologic Factors / genetics, pharmacology* Plant Viruses / genetics Recombinant Fusion Proteins / genetics, pharmacology Tobacco / genetics Tumor Necrosis Factor-alpha / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antibodies, Neutralizing; 0/Immunoglobulin Light Chains; 0/Immunologic Factors; 0/Recombinant Fusion Proteins; 0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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