7df1
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7df1]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DF1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DF1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7df1]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DF1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DF1 FirstGlance]. <br> | ||
| - | </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=7df1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7df1 OCA], [https://pdbe.org/7df1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7df1 RCSB], [https://www.ebi.ac.uk/pdbsum/7df1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7df1 ProSAT]</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]] 2.806Å</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=7df1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7df1 OCA], [https://pdbe.org/7df1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7df1 RCSB], [https://www.ebi.ac.uk/pdbsum/7df1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7df1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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The cell-surface glycoprotein CD98-a subunit of the LAT1/CD98 amino acid transporter-is an attractive target for cancer immunotherapies, but its widespread expression has hampered the development of CD98-targeting antibody therapeutics. Here we report that an anti-CD98 antibody, identified via the screening of phage-display libraries of CD98 single-chain variable fragments with mutated complementarity-determining regions, preserves the physiological function of CD98 and elicits broad-spectrum crystallizable-fragment (Fc)-mediated anti-tumour activity (requiring Fcgamma receptors for immunoglobulins, macrophages, dendritic cells and CD8(+) T cells, as well as other components of the innate and adaptive immune systems) in multiple xenograft and syngeneic tumour models established in CD98-humanized mice. We also show that a variant of the anti-CD98 antibody with pH-dependent binding, generated by solving the structure of the antibody-CD98 complex, displayed enhanced tumour-specific activity and pharmacokinetics. pH-dependent antibody variants targeting widely expressed antigens may lead to superior therapeutic outcomes. | The cell-surface glycoprotein CD98-a subunit of the LAT1/CD98 amino acid transporter-is an attractive target for cancer immunotherapies, but its widespread expression has hampered the development of CD98-targeting antibody therapeutics. Here we report that an anti-CD98 antibody, identified via the screening of phage-display libraries of CD98 single-chain variable fragments with mutated complementarity-determining regions, preserves the physiological function of CD98 and elicits broad-spectrum crystallizable-fragment (Fc)-mediated anti-tumour activity (requiring Fcgamma receptors for immunoglobulins, macrophages, dendritic cells and CD8(+) T cells, as well as other components of the innate and adaptive immune systems) in multiple xenograft and syngeneic tumour models established in CD98-humanized mice. We also show that a variant of the anti-CD98 antibody with pH-dependent binding, generated by solving the structure of the antibody-CD98 complex, displayed enhanced tumour-specific activity and pharmacokinetics. pH-dependent antibody variants targeting widely expressed antigens may lead to superior therapeutic outcomes. | ||
| - | An anti-CD98 antibody displaying pH-dependent Fc-mediated tumour-specific activity against multiple cancers in CD98-humanized mice.,Tian X, Liu X, Ding J, Wang F, Wang K, Liu J, Wei Z, Hao X, Li Y, Wei X, Zhang H, Sui J Nat Biomed Eng. | + | An anti-CD98 antibody displaying pH-dependent Fc-mediated tumour-specific activity against multiple cancers in CD98-humanized mice.,Tian X, Liu X, Ding J, Wang F, Wang K, Liu J, Wei Z, Hao X, Li Y, Wei X, Zhang H, Sui J Nat Biomed Eng. 2023 Jan;7(1):8-23. doi: 10.1038/s41551-022-00956-5. Epub 2022 , Nov 24. PMID:36424464<ref>PMID:36424464</ref> |
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 7df1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7df1" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal structure of human CD98 heavy chain extracellular domain in complex with S1-F4 scFv
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Categories: Homo sapiens | Large Structures | Ding J | Liu X | Sui J | Tian X
