CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy

Activation of the adenosine receptor A2AR is associated with suppression of T cell function in the tumor microenvironment. To overcome immunosuppression, here the authors show that CRISPR/Cas9 mediated deletion of A2AR enhances CAR T cell effector functions without altering memory or persistence pro...

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Main Authors:	Lauren Giuffrida, Kevin Sek, Melissa A. Henderson, Junyun Lai, Amanda X. Y. Chen, Deborah Meyran, Kirsten L. Todd, Emma V. Petley, Sherly Mardiana, Christina Mølck, Gregory D. Stewart, Benjamin J. Solomon, Ian A. Parish, Paul J. Neeson, Simon J. Harrison, Lev M. Kats, Imran G. House, Phillip K. Darcy, Paul A. Beavis
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-05-01
Series:	Nature Communications
Online Access:	https://doi.org/10.1038/s41467-021-23331-5

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spelling	doaj-483b1c1b715b445cad3cbef377ef84662021-05-30T11:12:58ZengNature Publishing GroupNature Communications2041-17232021-05-0112111810.1038/s41467-021-23331-5CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacyLauren Giuffrida0Kevin Sek1Melissa A. Henderson2Junyun Lai3Amanda X. Y. Chen4Deborah Meyran5Kirsten L. Todd6Emma V. Petley7Sherly Mardiana8Christina Mølck9Gregory D. Stewart10Benjamin J. Solomon11Ian A. Parish12Paul J. Neeson13Simon J. Harrison14Lev M. Kats15Imran G. House16Phillip K. Darcy17Paul A. Beavis18Cancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreDepartment of Pathology, University of MelbourneDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversitySir Peter MacCallum Department of Oncology, The University of MelbourneCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreSir Peter MacCallum Department of Oncology, The University of MelbourneSir Peter MacCallum Department of Oncology, The University of MelbourneCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreCancer Immunology Program, Peter MacCallum Cancer CentreActivation of the adenosine receptor A2AR is associated with suppression of T cell function in the tumor microenvironment. To overcome immunosuppression, here the authors show that CRISPR/Cas9 mediated deletion of A2AR enhances CAR T cell effector functions without altering memory or persistence properties, improving CAR-T mediated tumor control in pre-clinical models.https://doi.org/10.1038/s41467-021-23331-5
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Lauren Giuffrida Kevin Sek Melissa A. Henderson Junyun Lai Amanda X. Y. Chen Deborah Meyran Kirsten L. Todd Emma V. Petley Sherly Mardiana Christina Mølck Gregory D. Stewart Benjamin J. Solomon Ian A. Parish Paul J. Neeson Simon J. Harrison Lev M. Kats Imran G. House Phillip K. Darcy Paul A. Beavis
spellingShingle	Lauren Giuffrida Kevin Sek Melissa A. Henderson Junyun Lai Amanda X. Y. Chen Deborah Meyran Kirsten L. Todd Emma V. Petley Sherly Mardiana Christina Mølck Gregory D. Stewart Benjamin J. Solomon Ian A. Parish Paul J. Neeson Simon J. Harrison Lev M. Kats Imran G. House Phillip K. Darcy Paul A. Beavis CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy Nature Communications
author_facet	Lauren Giuffrida Kevin Sek Melissa A. Henderson Junyun Lai Amanda X. Y. Chen Deborah Meyran Kirsten L. Todd Emma V. Petley Sherly Mardiana Christina Mølck Gregory D. Stewart Benjamin J. Solomon Ian A. Parish Paul J. Neeson Simon J. Harrison Lev M. Kats Imran G. House Phillip K. Darcy Paul A. Beavis
author_sort	Lauren Giuffrida
title	CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy
title_short	CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy
title_full	CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy
title_fullStr	CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy
title_full_unstemmed	CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy
title_sort	crispr/cas9 mediated deletion of the adenosine a2a receptor enhances car t cell efficacy
publisher	Nature Publishing Group
series	Nature Communications
issn	2041-1723
publishDate	2021-05-01
description	Activation of the adenosine receptor A2AR is associated with suppression of T cell function in the tumor microenvironment. To overcome immunosuppression, here the authors show that CRISPR/Cas9 mediated deletion of A2AR enhances CAR T cell effector functions without altering memory or persistence properties, improving CAR-T mediated tumor control in pre-clinical models.
url	https://doi.org/10.1038/s41467-021-23331-5
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CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy

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