Document Detail


Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties.
MedLine Citation:
PMID:  23211638     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several novel anti-CD20 monoclonal antibodies are currently in development with the aim of improving the treatment of B cell malignancies. Mutagenesis and epitope mapping studies have revealed differences between the CD20 epitopes recognized by these antibodies. Recently, X-ray crystallography studies confirmed that the Type I CD20 antibody rituximab and the Type II CD20 antibody obinutuzumab (GA101) differ fundamentally in their interaction with CD20 despite recognizing a partially overlapping epitope on CD20. The Type I CD20 antibodies rituximab and ofatumumab are known to bind to different epitopes. The differences suggest that the biological properties of these antibodies are not solely determined by their core epitope sequences, but also depend on other factors, such as the elbow hinge angle, the orientation of the bound antibody and differential effects mediated by the Fc region of the antibody. Taken together, these factors may explain differences in the preclinical properties and clinical efficacy of anti-CD20 antibodies.
Authors:
Christian Klein; Alfred Lammens; Wolfgang Schäfer; Guy Georges; Manfred Schwaiger; Ekkehard Mössner; Karl-Peter Hopfner; Pablo Umaña; Gerhard Niederfellner
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Publication Detail:
Type:  Journal Article     Date:  2012-12-04
Journal Detail:
Title:  mAbs     Volume:  5     ISSN:  1942-0870     ISO Abbreviation:  MAbs     Publication Date:    2013 Jan-Feb
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-07-15     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  101479829     Medline TA:  MAbs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22-33     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antibodies, Monoclonal / immunology,  metabolism*,  therapeutic use
Antibodies, Monoclonal, Humanized / immunology,  metabolism,  therapeutic use
Antibodies, Monoclonal, Murine-Derived / immunology,  metabolism,  therapeutic use
Antigens, CD20 / chemistry,  genetics,  immunology,  metabolism*
Clinical Trials as Topic
Crystallography, X-Ray
Epitope Mapping
Epitopes / chemistry,  immunology,  metabolism*
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / therapy
Lymphoma, Non-Hodgkin / therapy
Mice
Models, Molecular
Molecular Sequence Data
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antibodies, Monoclonal, Murine-Derived; 0/Antigens, CD20; 0/Epitopes; 0/ofatumumab; 0/rituximab; O43472U9X8/obinutuzumab
Comments/Corrections
Comment In:
MAbs. 2013 May-Jun;5(3):337-8   [PMID:  23493087 ]
MAbs. 2013 May-Jun;5(3):335-6   [PMID:  23493149 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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