| Obtention and engineering of non-human primate (NHP) antibodies for therapeutics. | |
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MedLine Citation:
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PMID: 20105119 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recombinant antibodies are therapeutic molecules of choice regarding their efficacy, pharmacokinetics and tolerance - all the more if they are human. The efficacy of antibodies generally depends on their affinity for their antigens. The most straightforward approach to isolate human antibodies with high affinities is the construction and screening of human immune libraries, but Humans cannot be immunized with all antigens of interest, for ethical and practical reasons. We circumvented that difficulty by utilizing non-human primates (NHP) instead of Humans and, in the course of our different studies, we have obtained several antibody fragments with high or very high affinities (from 3 nM to 50 pM) and neutralizing properties. The framework regions (FR) - the regions most implicated in tolerance - of these NHP antibody fragments were shown to be very similar to FR encoded by human germline genes. In one case, in a process called "germline humanization" (or "super-humanization"), we have increased that level of similarity and managed to go even beyond the level observed for human antibodies, without any loss of affinity. Here, the methodological peculiarities of our approach, in comparison with immune libraries built from immunised Humans, and the rationales behind these peculiarities, will be reviewed. The isolation of NHP antibody fragments from immune libraries, followed by the "super-humanization" process, opens a new and highly efficient approach for the production of high-quality recombinant antibodies for therapeutic uses. |
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Authors:
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Thibaut Pelat; Michael Hust; Philippe Thullier |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Mini reviews in medicinal chemistry Volume: 9 ISSN: 1875-5607 ISO Abbreviation: Mini Rev Med Chem Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2010-03-19 Completed Date: 2010-06-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101094212 Medline TA: Mini Rev Med Chem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1633-8 Citation Subset: IM |
Affiliation:
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D?partement de biologie des agents transmissibles, Centre de Recherche du Service de Sant? des Arm?es, La Tronche, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies / genetics, immunology, therapeutic use* Genetic Engineering* Humans Immunoglobulin Variable Region / genetics Peptide Library Primates / immunology* Recombinant Proteins / genetics, immunology, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Immunoglobulin Variable Region; 0/Peptide Library; 0/Recombinant Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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