View source for 6txz


==FAB PART OF M6903 IN COMPLEX WITH HUMAN TIM3==
<StructureSection load='6txz' size='340' side='right'caption='[[6txz]], [[Resolution|resolution]] 3.06&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6txz]] 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=6TXZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TXZ 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]] 3.06&#8491;</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=6txz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6txz OCA], [https://pdbe.org/6txz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6txz RCSB], [https://www.ebi.ac.uk/pdbsum/6txz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6txz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HAVR2_HUMAN HAVR2_HUMAN] Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9.<ref>PMID:14556005</ref> <ref>PMID:16286920</ref> 
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== Publication Abstract from PubMed ==
T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune checkpoint that regulates normal immune responses but can be exploited by tumor cells to evade immune surveillance. TIM-3 is primarily expressed on immune cells, particularly on dysfunctional and exhausted T cells, and engagement of TIM-3 with its ligands promotes TIM-3-mediated T cell inhibition. Antagonistic ligand-blocking anti-TIM-3 antibodies have the potential to abrogate T cell inhibition, activate antigen-specific T cells, and enhance anti-tumor immunity. Here we describe M6903, a fully human anti-TIM-3 antibody without effector function and with high affinity and selectivity to TIM-3. We demonstrate that M6903 blocks the binding of TIM-3 to three of its ligands, phosphatidylserine (PtdSer), carcinoembryonic antigen cell adhesion-related molecule 1 (CEACAM1), and galectin 9 (Gal-9). These results are supported by an atomic resolution crystal structure and functional assays, which demonstrate that M6903 monotherapy enhanced T cell activation. This activation was further enhanced by the combination of M6903 with bintrafusp alfa, a bifunctional fusion protein that simultaneously blocks the transforming growth factor-beta (TGF-beta) and programmed death ligand 1 (PD-L1) pathways. M6903 and bintrafusp alfa combination therapy also enhanced anti-tumor efficacy in huTIM-3 knock-in mice, relative to either monotherapy. These in vitro and in vivo data, along with favorable pharmacokinetics in marmoset monkeys, suggest that M6903 as a monotherapy warrants further pre-clinical assessment and that M6903 and bintrafusp alfa may be a promising combination therapy in the clinic.

Identification and characterization of M6903, an antagonistic anti-TIM-3 monoclonal antibody.,Zhang D, Jiang F, Zaynagetdinov R, Huang H, Sood VD, Wang H, Zhao X, Jenkins MH, Ji Q, Wang Y, Nannemann DP, Musil D, Wesolowski J, Paoletti A, Bartholomew T, Derner MG, An Q, Iffland C, Halle JP Oncoimmunology. 2020 Apr 1;9(1):1744921. doi: 10.1080/2162402X.2020.1744921., eCollection 2020. PMID:32313722<ref>PMID:32313722</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6txz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Musil D]]
[[Category: Sood V]]