Document Detail


Obtention and engineering of non-human primate (NHP) antibodies for therapeutics.
MedLine Citation:
PMID:  20105119     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Thibaut Pelat; Michael Hust; Philippe Thullier
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Mini reviews in medicinal chemistry     Volume:  9     ISSN:  1875-5607     ISO Abbreviation:  Mini Rev Med Chem     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2010-03-19     Completed Date:  2010-06-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101094212     Medline TA:  Mini Rev Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1633-8     Citation Subset:  IM    
Affiliation:
D?partement de biologie des agents transmissibles, Centre de Recherche du Service de Sant? des Arm?es, La Tronche, France.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Antibodies; 0/Immunoglobulin Variable Region; 0/Peptide Library; 0/Recombinant Proteins

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