A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3

TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion of inflamm...

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Autores principales: Zwolak, Adam, Chan, Szeman Ruby, Harvilla, Paul, Mahady, Sally, Armstrong, Anthony A., Luistro, Leopoldo, Tamot, Ninkka, Yamada, Douglas, Derebe, Mehabaw, Pomerantz, Steven, Chiu, Mark, Ganesan, Rajkumar, Chowdhury, Partha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709071/
https://www.ncbi.nlm.nih.gov/pubmed/36446890
http://dx.doi.org/10.1038/s41598-022-24984-y
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author Zwolak, Adam
Chan, Szeman Ruby
Harvilla, Paul
Mahady, Sally
Armstrong, Anthony A.
Luistro, Leopoldo
Tamot, Ninkka
Yamada, Douglas
Derebe, Mehabaw
Pomerantz, Steven
Chiu, Mark
Ganesan, Rajkumar
Chowdhury, Partha
author_facet Zwolak, Adam
Chan, Szeman Ruby
Harvilla, Paul
Mahady, Sally
Armstrong, Anthony A.
Luistro, Leopoldo
Tamot, Ninkka
Yamada, Douglas
Derebe, Mehabaw
Pomerantz, Steven
Chiu, Mark
Ganesan, Rajkumar
Chowdhury, Partha
author_sort Zwolak, Adam
collection PubMed
description TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion of inflammatory cytokines. We designed a stable recombinant TL1A molecule that (1) displays high monodispersity and stability, (2) displays the ability to activate T cells in vitro and in vivo, and (3) lacks binding to DcR3 while retaining functional activity via DR3. Together these results suggest the TL1A ligand can be amenable to therapeutic development on its own or paired with a tumor-targeting moiety.
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spelling pubmed-97090712022-12-01 A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3 Zwolak, Adam Chan, Szeman Ruby Harvilla, Paul Mahady, Sally Armstrong, Anthony A. Luistro, Leopoldo Tamot, Ninkka Yamada, Douglas Derebe, Mehabaw Pomerantz, Steven Chiu, Mark Ganesan, Rajkumar Chowdhury, Partha Sci Rep Article TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion of inflammatory cytokines. We designed a stable recombinant TL1A molecule that (1) displays high monodispersity and stability, (2) displays the ability to activate T cells in vitro and in vivo, and (3) lacks binding to DcR3 while retaining functional activity via DR3. Together these results suggest the TL1A ligand can be amenable to therapeutic development on its own or paired with a tumor-targeting moiety. Nature Publishing Group UK 2022-11-29 /pmc/articles/PMC9709071/ /pubmed/36446890 http://dx.doi.org/10.1038/s41598-022-24984-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zwolak, Adam
Chan, Szeman Ruby
Harvilla, Paul
Mahady, Sally
Armstrong, Anthony A.
Luistro, Leopoldo
Tamot, Ninkka
Yamada, Douglas
Derebe, Mehabaw
Pomerantz, Steven
Chiu, Mark
Ganesan, Rajkumar
Chowdhury, Partha
A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3
title A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3
title_full A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3
title_fullStr A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3
title_full_unstemmed A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3
title_short A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3
title_sort stable, engineered tl1a ligand co-stimulates t cells via specific binding to dr3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709071/
https://www.ncbi.nlm.nih.gov/pubmed/36446890
http://dx.doi.org/10.1038/s41598-022-24984-y
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