6ba5: Difference between revisions

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'''Unreleased structure'''


The entry 6ba5 is ON HOLD until Paper Publication
==Potent and Selective Antitumor Activity of a T-Cell Engaging Bispecific Antibody Targeting a Membrane-Proximal Epitope of ROR1==
<StructureSection load='6ba5' size='340' side='right' caption='[[6ba5]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ba5]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BA5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BA5 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=6ba5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ba5 OCA], [http://pdbe.org/6ba5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ba5 RCSB], [http://www.ebi.ac.uk/pdbsum/6ba5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ba5 ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/ROR1_HUMAN ROR1_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[[http://www.uniprot.org/uniprot/ROR1_HUMAN ROR1_HUMAN]] Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350).<ref>PMID:25029443</ref> <ref>PMID:27162350</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
T cell-engaging bispecific antibodies (biAbs) present a promising strategy for cancer immunotherapy, and numerous bispecific formats have been developed for retargeting cytolytic T cells toward tumor cells. To explore the therapeutic utility of T cell-engaging biAbs targeting the receptor tyrosine kinase ROR1, which is expressed by tumor cells of various hematologic and solid malignancies, we used a bispecific ROR1 x CD3 scFv-Fc format based on a heterodimeric and aglycosylated Fc domain designed for extended circulatory t1/2 and diminished systemic T cell activation. A diverse panel of ROR1-targeting scFv derived from immune and naive rabbit antibody repertoires was compared in this bispecific format for target-dependent T cell recruitment and activation. An ROR1-targeting scFv with a membrane-proximal epitope, R11, revealed potent and selective antitumor activity in vitro, in vivo, and ex vivo and emerged as a prime candidate for further preclinical and clinical studies. To elucidate the precise location and engagement of this membrane-proximal epitope, which is conserved between human and mouse ROR1, the 3D structure of scFv R11 in complex with the kringle domain of ROR1 was determined by X-ray crystallography at 1.6-A resolution.


Authors: Park, H., Rader, C.
Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1.,Qi J, Li X, Peng H, Cook EM, Dadashian EL, Wiestner A, Park H, Rader C Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5467-E5476. doi:, 10.1073/pnas.1719905115. Epub 2018 May 29. PMID:29844189<ref>PMID:29844189</ref>


Description: Potent and Selective Antitumor Activity of a T-Cell Engaging Bispecific Antibody Targeting a Membrane-Proximal Epitope of ROR1
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6ba5" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Park, H]]
[[Category: Rader, C]]
[[Category: Rader, C]]
[[Category: Park, H]]
[[Category: Antibody]]
[[Category: Immune system]]
[[Category: Kringle domain]]
[[Category: Phage display]]
[[Category: Receptor tyrosine kinase-like orphan receptor]]
[[Category: Ror1]]
[[Category: Scfv]]
[[Category: Single chain fv]]
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