Titre
Survivin-specific T cell receptor targets tumor but not T cells.
Type
article
Institution
Externe
Périodique
Auteur(s)
Arber, C.
Auteure/Auteur
Feng, X.
Auteure/Auteur
Abhyankar, H.
Auteure/Auteur
Romero, E.
Auteure/Auteur
Wu, M.F.
Auteure/Auteur
Heslop, H.E.
Auteure/Auteur
Barth, P.
Auteure/Auteur
Dotti, G.
Auteure/Auteur
Savoldo, B.
Auteure/Auteur
Liens vers les personnes
ISSN
1558-8238
Statut éditorial
Publié
Date de publication
2015-01
Volume
125
Numéro
1
Première page
157
Dernière page/numéro d’article
168
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Publication Status: ppublish
Résumé
Survivin is a tumor-associated antigen (TAA) that inhibits apoptosis and is widely overexpressed in cancer cells; therefore, survivin has potential as a target for cancer immunotherapy. Application of HLA-A2-restricted survivin-specific T cell receptors (TCRs) isolated from allogeneic HLA-mismatched TCR repertoires has, however, been impeded by the inability of these TCRs to distinguish healthy cells expressing low levels of survivin from cancer cells with high survivin expression levels. Here, we identified an HLA-A2-restricted survivin-specific TCR isolated from autologous TCR repertoires that targets tumor cells in vitro and in vivo but does not cause fratricidal toxicity. Molecular modeling of the TCR-peptide-HLA ternary complexes and alanine scanning revealed that the autologously derived TCRs had tighter interactions with the survivin peptide than did fratricidal TCRs. Similar recognition patterns were observed among 7 additional TAA-specific TCRs isolated from allogeneic versus autologous repertoires. Together, the results from this study indicate that maximal peptide recognition is key for TCR selectivity and likely critical for reducing unwanted off-target toxicities. Moreover, isolating TCRs from autologous repertoires to maximize TCR selectivity has potential as a useful strategy to identify and select other shared tumor- and self-antigen-specific TCRs and ensure selective antitumor activity.
PID Serval
serval:BIB_955706244B8D
PMID
Open Access
Oui
Date de création
2019-11-01T08:56:10.139Z
Date de création dans IRIS
2025-05-20T22:38:39Z
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Nom
Arber et al-JCI-2015.pdf
Version du manuscrit
preprint
Taille
3.5 MB
Format
Adobe PDF
PID Serval
serval:BIB_955706244B8D.S001
Somme de contrôle
(MD5):f219b8e4fc774f74def50fc7d186cbc2