Determinants of response and resistance to CAR T cell therapy.
Journal
Seminars in cancer biology
ISSN: 1096-3650
Titre abrégé: Semin Cancer Biol
Pays: England
ID NLM: 9010218
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
30
09
2019
revised:
28
10
2019
accepted:
03
11
2019
pubmed:
11
11
2019
medline:
9
6
2021
entrez:
10
11
2019
Statut:
ppublish
Résumé
The remarkable success of chimeric antigen receptor (CAR)-engineered T cells in pre-B cell acute lymphoblastic leukemia (ALL) and B cell lymphoma led to the approval of anti-CD19 CAR T cells as the first ever CAR T cell therapy in 2017. However, with the number of CAR T cell-treated patients increasing, observations of tumor escape and resistance to CAR T cell therapy with disease relapse are demonstrating the current limitations of this therapeutic modality. Mechanisms hampering CAR T cell efficiency include limited T cell persistence, caused for example by T cell exhaustion and activation-induced cell death (AICD), as well as therapy-related toxicity. Furthermore, the physical properties, antigen heterogeneity and immunosuppressive capacities of solid tumors have prevented the success of CAR T cells in these entities. Herein we review current obstacles of CAR T cell therapy and propose strategies in order to overcome these hurdles and expand CAR T cell therapy to a broader range of cancer patients.
Identifiants
pubmed: 31705998
pii: S1044-579X(19)30219-6
doi: 10.1016/j.semcancer.2019.11.004
pii:
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
80-90Subventions
Organisme : European Research Council
ID : 756017
Pays : International
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.