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| | ==Generation and Characterization of a Unique Reagent that Recognizes a Panel of Recombinant Human Monoclonal Antibody Therapeutics in the Presence of Endogenous Human IgG== | | ==Generation and Characterization of a Unique Reagent that Recognizes a Panel of Recombinant Human Monoclonal Antibody Therapeutics in the Presence of Endogenous Human IgG== |
| - | <StructureSection load='4k7p' size='340' side='right' caption='[[4k7p]], [[Resolution|resolution]] 2.95Å' scene=''> | + | <StructureSection load='4k7p' size='340' side='right'caption='[[4k7p]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k7p]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Rhizidium_phycophilum Rhizidium phycophilum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K7P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K7P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k7p]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K7P FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k7p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k7p RCSB], [http://www.ebi.ac.uk/pdbsum/4k7p PDBsum]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4k7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k7p OCA], [https://pdbe.org/4k7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k7p RCSB], [https://www.ebi.ac.uk/pdbsum/4k7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k7p ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4k7p" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Monoclonal Antibody|Monoclonal Antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Rhizidium phycophilum]]
| + | [[Category: Eigenbrot C]] |
| - | [[Category: Eigenbrot, C]] | + | [[Category: Shia S]] |
| - | [[Category: Shia, S]] | + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Pharmacokinetic (PK) and immunohistochemistry (IHC) assays are essential to the evaluation of the safety and efficacy of therapeutic monoclonal antibodies (mAb) during drug development. These methods require reagents with a high degree of specificity because low concentrations of therapeutic antibody need to be detected in samples containing high concentrations of endogenous human immunoglobulins. Current assay reagent generation practices are labor-intensive and time-consuming. Moreover, these practices are molecule-specific and so only support one assay for one program at a time. Here, we describe a strategy to generate a unique assay reagent, 10C4, that preferentially recognizes a panel of recombinant human mAbs over endogenous human immunoglobulins. This "panel-specific" feature enables the reagent to be used in PK and IHC assays for multiple structurally-related therapeutic mAbs. Characterization revealed that the 10C4 epitope is conformational, extensive and mainly composed of non-CDR residues. Most key contact residues were conserved among structurally-related therapeutic mAbs, but the combination of these residues exists at low prevalence in endogenous human immunoglobulins. Interestingly, an indirect contact residue on the heavy chain of the therapeutic appears to play a critical role in determining whether or not it can bind to 10C4, but has no affect on target binding. This may allow us to improve the binding of therapeutic mAbs to 10C4 for assay development in the future. Here, for the first time, we present a strategy to develop a panel-specific reagent that can expedite the development of multiple clinical assays for structurally-related therapeutic mAbs.
Generation and characterization of a unique reagent that recognizes a panel of recombinant human monoclonal antibody therapeutics in the presence of endogenous human IgG.,Wang X, Quarmby V, Ng C, Chuntharapai A, Shek T, Eigenbrot C, Kelley RF, Shia S, McCutcheon K, Lowe J, Leddy C, Coachman K, Cain G, Chu F, Hotzel I, Maia M, Wakshull E, Yang J MAbs. 2013 Jul 1;5(4):540-54. doi: 10.4161/mabs.24822. Epub 2013 Apr 29. PMID:23774668[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang X, Quarmby V, Ng C, Chuntharapai A, Shek T, Eigenbrot C, Kelley RF, Shia S, McCutcheon K, Lowe J, Leddy C, Coachman K, Cain G, Chu F, Hotzel I, Maia M, Wakshull E, Yang J. Generation and characterization of a unique reagent that recognizes a panel of recombinant human monoclonal antibody therapeutics in the presence of endogenous human IgG. MAbs. 2013 Jul 1;5(4):540-54. doi: 10.4161/mabs.24822. Epub 2013 Apr 29. PMID:23774668 doi:10.4161/mabs.24822
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