Physiological lentiviral vectors for the generation of improved CAR-T cells.
CAR-T
T cells phenotype
TCR-like expression
WAS gene promoter
exhaustion
lentiviral vectors
leukemia
lymphoma
physiological expression
tonic signaling
Journal
Molecular therapy oncolytics
ISSN: 2372-7705
Titre abrégé: Mol Ther Oncolytics
Pays: United States
ID NLM: 101666776
Informations de publication
Date de publication:
16 Jun 2022
16 Jun 2022
Historique:
received:
15
11
2021
accepted:
07
05
2022
entrez:
13
6
2022
pubmed:
14
6
2022
medline:
14
6
2022
Statut:
epublish
Résumé
Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a
Identifiants
pubmed: 35694446
doi: 10.1016/j.omto.2022.05.003
pii: S2372-7705(22)00068-7
pmc: PMC9163403
doi:
Types de publication
Journal Article
Langues
eng
Pagination
335-349Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
F.M., M.T.-M., N.M.-P., P.M., and K.B. are inventors of the patent entitled “Polynucleotide for safer and more effective immunotherapies for CAR-T cells applications” (PCT/EP2019/081346). P.-J.L. and M.T.-M. are contractually associated with LentiStem Biotech, a spin-off company that acquired the license for the PCT/EP2019/081346 patent. F.M. is an owner (>5%) of LentiStem Biotech. LentiStem Biotech partially funded this work through a Neotec Project (CDTI exp: SNEO-20191072). The rest of the authors declare no competing interests.
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