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

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_799B70627D11
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
CART cells are prone to Fas- and DR5-mediated cell death.
Périodique
Journal for immunotherapy of cancer
Auteur(s)
Tschumi B.O., Dumauthioz N., Marti B., Zhang L., Schneider P., Mach J.P., Romero P., Donda A.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Statut éditorial
Publié
Date de publication
13/07/2018
Peer-reviewed
Oui
Volume
6
Numéro
1
Pages
71
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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.
Mots-clé
4-1BB, Annexin V, CAR T cells, CD28, CD3ζ, CD8 T lymphocytes, Fas, FasL, HER2, Listeria monocytogenes
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/08/2018 8:40
Dernière modification de la notice
20/08/2019 14:36
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