7vux: Difference between revisions
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==Complex structure of PD1 and 609A-Fab== | |||
<StructureSection load='7vux' size='340' side='right'caption='[[7vux]], [[Resolution|resolution]] 1.64Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7vux]] is a 3 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=7VUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VUX FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.64Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=THR:THREONINE'>THR</scene></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=7vux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vux OCA], [https://pdbe.org/7vux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vux RCSB], [https://www.ebi.ac.uk/pdbsum/7vux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vux ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Targeting PD1/PDL1 with blocking antibodies for cancer therapy has shown promising benefits in the clinic, but only approximately 20-30% of patients develop durable clinical responses to the treatment. Bispecific antibodies (BsAbs) that combine PD1/PDL1 blockade with the modulation of another immune checkpoint target may have greater potential to enhance immune checkpoint blockade therapy. In this study, we identified an anti-PD1 monoclonal antibody, 609A, whose heavy chain can pair with a variety of light chains from different antibodies while maintaining its PD1 binding/blocking activity. Taking advantage of this property and using a linear F(ab')(2) format, we successfully produced a series of tetravalent IgG-like BsAbs that simultaneously target PD1 and other immune checkpoint targets, including PDL1 and CTLA4. The BsAbs exhibited superior bioactivities in vitro and in vivo compared to their respective parental mAbs. Importantly, the BsAbs demonstrated the desired IgG-like physicochemical properties in terms of high-level expression, ease of purification to homogeneity, good stability and in vivo pharmacokinetics. In summary, we describe a novel and flexible plug-and-play platform to engineer IgG-like BsAbs with excellent development potential for clinical applications. | |||
A strategy for the efficient construction of anti-PD1-based bispecific antibodies with desired IgG-like properties.,Zhao J, Jiang L, Yang H, Deng L, Meng X, Ding J, Yang S, Zhao L, Xu W, Wang X, Zhu Z, Huang H MAbs. 2022 Jan-Dec;14(1):2044435. doi: 10.1080/19420862.2022.2044435. PMID:35239451<ref>PMID:35239451</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7vux" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Antibody 3D structures|Antibody 3D structures]] | ||
[[Category: | *[[Cell death protein 3D structures|Cell death protein 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Deng L]] | ||
[[Category: Ding J]] | |||
[[Category: Huang H]] | |||
[[Category: Jiang L]] | |||
[[Category: Meng X]] | |||
[[Category: Wang X]] | |||
[[Category: Xu W]] | |||
[[Category: Yang H]] | |||
[[Category: Yang S]] | |||
[[Category: Zhao J]] | |||
[[Category: Zhao L]] | |||
[[Category: Zhu Z]] | |||
Latest revision as of 12:17, 17 October 2024
Complex structure of PD1 and 609A-FabComplex structure of PD1 and 609A-Fab
Structural highlights
Publication Abstract from PubMedTargeting PD1/PDL1 with blocking antibodies for cancer therapy has shown promising benefits in the clinic, but only approximately 20-30% of patients develop durable clinical responses to the treatment. Bispecific antibodies (BsAbs) that combine PD1/PDL1 blockade with the modulation of another immune checkpoint target may have greater potential to enhance immune checkpoint blockade therapy. In this study, we identified an anti-PD1 monoclonal antibody, 609A, whose heavy chain can pair with a variety of light chains from different antibodies while maintaining its PD1 binding/blocking activity. Taking advantage of this property and using a linear F(ab')(2) format, we successfully produced a series of tetravalent IgG-like BsAbs that simultaneously target PD1 and other immune checkpoint targets, including PDL1 and CTLA4. The BsAbs exhibited superior bioactivities in vitro and in vivo compared to their respective parental mAbs. Importantly, the BsAbs demonstrated the desired IgG-like physicochemical properties in terms of high-level expression, ease of purification to homogeneity, good stability and in vivo pharmacokinetics. In summary, we describe a novel and flexible plug-and-play platform to engineer IgG-like BsAbs with excellent development potential for clinical applications. A strategy for the efficient construction of anti-PD1-based bispecific antibodies with desired IgG-like properties.,Zhao J, Jiang L, Yang H, Deng L, Meng X, Ding J, Yang S, Zhao L, Xu W, Wang X, Zhu Z, Huang H MAbs. 2022 Jan-Dec;14(1):2044435. doi: 10.1080/19420862.2022.2044435. PMID:35239451[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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