CART cells are prone to Fas- and DR5-mediated cell death

Journal for Immunotherapy of Cancer
Benjamin O TschumiAlena Donda

Abstract

Adoptive transfer of T cells transduced with Chimeric Antigen Receptors (CAR) are now FDA-approved for the treatment of B-cell malignancies. Yet, the functionality of the endogenous TCR in CART cells has not been fully assessed. Here, we demonstrate that CART cells progressively upregulate Fas, FasL, DR5 and TRAIL, which result in their programmed cell death, independently of antigen-mediated TCR or CAR activation. CART cell apoptosis occurs even when the CAR contains a single (co-)activatory domain such as CD3ζ, CD28 or 4-1BB. Importantly, the dominant role of the Fas and DR5 pathways in CART cell apoptosis is demonstrated by the significant rescue of CART cells upon in vivo blockade by combined Fas-Fc and DR5-Fc recombinant proteins. These observations are of crucial importance for the long-term persistence of CART cells and for the development of new applications including the combined TCR and CAR activation against solid tumors.

References

May 16, 1995·International Journal of Cancer. Journal International Du Cancer·M J VerhaarR H Begent
Oct 21, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Regina TavanoAntonella Viola
Mar 21, 2006·The Journal of Biological Chemistry·Claudia BossenPascal Schneider
Jun 6, 2007·Seminars in Immunology·Michelle KrogsgaardMark M Davis
Feb 3, 2009·Nature·Dietmar ZehnMichael J Bevan
Mar 23, 2012·Nature Reviews. Immunology·Nicholas P RestifoSteven A Rosenberg
Mar 27, 2013·The New England Journal of Medicine·Stephan A GruppCarl H June
Oct 16, 2014·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Oct 28, 2015·Cancer Discovery·Aurore MorelloPrasad S Adusumilli
Dec 23, 2016·Immunology and Cell Biology·Carmen S M YongMichael H Kershaw
Dec 28, 2016·Cell Research·Laura A Johnson, Carl H June
Nov 7, 2017·Leukemia & Lymphoma·Arnab GhoshRenier J Brentjens
Nov 24, 2017·Science Translational Medicine·Yinmeng YangTerry J Fry

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Citations

Nov 9, 2018·Clinical Pharmacology and Therapeutics·Trevor R BaybuttAdam E Snook
Nov 26, 2019·Current Opinion in Hematology·Rosalie M Sterner, Saad S Kenderian
Dec 18, 2019·Briefings in Functional Genomics·Guillermo Ureña-BailénMarkus Mezger
Sep 18, 2020·Journal for Immunotherapy of Cancer·Semjon WillierTobias Feuchtinger
Sep 27, 2018·Journal for Immunotherapy of Cancer·Benjamin O TschumiAlena Donda
Jan 26, 2021·Frontiers in Oncology·Jiaqiao FanJianxun Song
Jan 1, 2021·Frontiers in Immunology·Yu ZhangPeng Jiang
Feb 28, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Claudia Manriquez-RomanSaad S Kenderian
Mar 26, 2021·Science Translational Medicine·Yue LiuXin Lin
Mar 25, 2021·Cancer Management and Research·David M RichardsAndriy Krendyukov
Oct 22, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tara Murty, Crystal L Mackall
Jan 16, 2022·Human Cell·Tian HuanFeng Yu

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Methods Mentioned

BETA
transfection
flow cytometry
FACS

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