8oz3: Difference between revisions

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'''Unreleased structure'''


The entry 8oz3 is ON HOLD
==Crystal structure of scFv ATOR 1017 bound to human 4-1BB==
<StructureSection load='8oz3' size='340' side='right'caption='[[8oz3]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8oz3]] is a 6 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=8OZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OZ3 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]] 3.1&#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=8oz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oz3 OCA], [https://pdbe.org/8oz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oz3 RCSB], [https://www.ebi.ac.uk/pdbsum/8oz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oz3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TNR9_HUMAN TNR9_HUMAN] Receptor for TNFSF9/4-1BBL. Possibly active during T cell activation.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: 4-1BB (CD137) is a co-stimulatory receptor highly expressed on tumor reactive effector T cells and NK cells, which upon stimulation prolongs persistence of tumor reactive effector T and NK cells within the tumor and induces long-lived memory T cells. 4-1BB agonistic antibodies have been shown to induce strong anti-tumor effects that synergize with immune checkpoint inhibitors. The first generation of 4-1BB agonists was, however, hampered by dose-limiting toxicities resulting in suboptimal dose levels or poor agonistic activity. METHODS: ATOR-1017 (evunzekibart), a second-generation Fc-gamma receptor conditional 4-1BB agonist in IgG4 format, was designed to overcome the limitations of the first generation of 4-1BB agonists, providing strong agonistic effect while minimizing systemic immune activation and risk of hepatoxicity. The epitope of ATOR-1017 was determined by X-ray crystallography, and the functional activity was assessed in vitro and in vivo as monotherapy or in combination with anti-PD1. RESULTS: ATOR-1017 binds to a unique epitope on 4-1BB enabling ATOR-1017 to activate T cells, including cells with an exhausted phenotype, and NK cells, in a cross-linking dependent, FcgammaR-conditional, manner. This translated into a tumor-directed and potent anti-tumor therapeutic effect in vivo, which was further enhanced with anti-PD-1 treatment. CONCLUSIONS: These preclinical data demonstrate a strong safety profile of ATOR-1017, together with its potent therapeutic effect as monotherapy and in combination with anti-PD1, supporting further clinical development of ATOR-1017.


Authors: Hakansson, M., Von Schantz, L., Rose, N.
ATOR-1017 (evunzekibart), an Fc-gamma receptor conditional 4-1BB agonist designed for optimal safety and efficacy, activates exhausted T cells in combination with anti-PD-1.,Enell Smith K, Fritzell S, Nilsson A, Barchan K, Rosen A, Schultz L, Varas L, Sall A, Rose N, Hakansson M, von Schantz L, Ellmark P Cancer Immunol Immunother. 2023 Dec;72(12):4145-4159. doi: , 10.1007/s00262-023-03548-7. Epub 2023 Oct 5. PMID:37796298<ref>PMID:37796298</ref>


Description: Crystal structure of scFv ATOR 1017 bound to human 4-1BB
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Von Schantz, L]]
<div class="pdbe-citations 8oz3" style="background-color:#fffaf0;"></div>
[[Category: Rose, N]]
== References ==
[[Category: Hakansson, M]]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hakansson M]]
[[Category: Rose N]]
[[Category: Von Schantz L]]
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