Genetic and pharmacological targeting of A2a receptor improves function of anti-mesothelin CAR T cells

Journal of Experimental & Clinical Cancer Research : CR
Elham MasoumiJamshid Hadjati

Abstract

CAR T cell-based therapies have shown promising results in hematological malignancies. Results of CAR T cell projects in solid tumors have been less impressive, and factors including lack of targetable antigens and immunosuppressive tumor microenvironment (TME) have been suggested as culprits. Adenosine, a metabolite which is highly produced in TME, is known to mediate the suppression of anti-tumor T cell responses via binding and signaling through adenosine 2a receptor (A2aR). In this study, the expression of A2aR and the effects of its activation on the function of fully human anti-mesothelin CAR T cells (MSLN-CAR T), were analyzed. Afterwards, the molecular and pharmacological means to overcome the inhibitory effects of A2aR signaling on CAR T cell function were used. This was performed by targeting A2aR expression in MSLN-CAR T cells using various anti-A2aR shRNA sequences embedded in the CAR vector and an A2aR pharmacological antagonist, SCH-58261. Statistical analyses were performed Prism 7 software. Our experiments showed significant A2aR upregulation on T cells during the CAR T cell production procedure (cell activation and transduction). Activation of adenosine signaling using adenosine analog led to the suppression of...Continue Reading

References

Mar 1, 1995·European Journal of Immunology·C VincentJ P Revillard
Aug 3, 2000·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·S Romagnani
Dec 9, 2000·Naunyn-Schmiedeberg's Archives of Pharmacology·K N Klotz
Feb 7, 2003·Current Topics in Medicinal Chemistry·Barbara CacciariGiampiero Spalluto
Sep 10, 2003·Journal of Leukocyte Biology·Rosa Maria AspalterHermann Maximilian Wolf
Aug 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Akio OhtaMichail Sitkovsky
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charles P SevignyMark D Okusa
Apr 27, 2007·Cancer Metastasis Reviews·Denise A Chan, Amato J Giaccia
Jan 30, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xin HuangXianzheng Zhou
Feb 9, 2008·Trends in Immunology·Margaret S Bynoe, Christophe Viret
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michail V SitkovskyAkio Ohta
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhengguo XiaoMatthew F Mescher
Oct 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Akio OhtaMichail Sitkovsky
Jun 17, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aled ClaytonZsuzsanna Tabi
Dec 13, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Angela M GreenJoanne L Flynn
Aug 1, 2015·FEBS Letters·María Rosa BonoDaniela Sauma
Apr 12, 2016·Frontiers in Immunology·Akio Ohta
Dec 21, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Farhad Jadidi-NiaraghJamshid Hadjati
Feb 7, 2017·The Journal of Clinical Investigation·Paul A BeavisPhillip K Darcy
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Samaneh ArabJamshid Hadjati
Jun 28, 2017·Cancer Research·Arabella YoungMark J Smyth
Jun 20, 2018·Journal for Immunotherapy of Cancer·Robert D Leone, Leisha A Emens
Nov 15, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carter M SuryadevaraLuis Sanchez-Perez
Dec 6, 2018·International Journal of Molecular Sciences·Kevin SekPaul A Beavis
Oct 12, 2019·Journal for Immunotherapy of Cancer·Beatris Mastelic-GavilletSelena Vigano

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Citations

Jun 20, 2020·Scandinavian Journal of Immunology·Emmanuelle BenardSébastien Wälchli
Jul 30, 2020·Cancers·Andriy ZhylkoAgnieszka Graczyk-Jarzynka
Sep 29, 2020·Frontiers in Immunology·Arezoo JamaliJessica Hartmann
Nov 11, 2020·Oncogene·Mansour PoorebrahimRolf Kiessling
Nov 13, 2020·Expert Opinion on Biological Therapy·Astero KlampatsaSteven M Albelda
Feb 17, 2021·Biomarker Research·Laura CastellettiJohn E J Rasko
Apr 4, 2021·Cancers·Ali Hosseini Rad S MAlexander D McLellan
May 30, 2021·Nature Communications·Lauren GiuffridaPaul A Beavis
May 28, 2021·Biologics : Targets & Therapy·Maya GloverJohn Maher
Aug 9, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Behnia AkbariHamid Reza Mirzaei
Sep 15, 2021·Technology in Cancer Research & Treatment·Cheng-You JiaDa Fu

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Methods Mentioned

BETA
flow cytometry
PCR
transfection
enzyme-linked immunosorbent assay
flowcytometry
ELISA

Software Mentioned

FlowJo

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