Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
30
03
2022
accepted:
20
01
2023
medline:
13
11
2023
pubmed:
15
3
2023
entrez:
14
3
2023
Statut:
ppublish
Résumé
Chimeric antigen receptor T cells (CAR-T cells) have emerged as a powerful treatment option for individuals with B cell malignancies but have yet to achieve success in treating acute myeloid leukemia (AML) due to a lack of safe targets. Here we leveraged an atlas of publicly available RNA-sequencing data of over 500,000 single cells from 15 individuals with AML and tissue from 9 healthy individuals for prediction of target antigens that are expressed on malignant cells but lacking on healthy cells, including T cells. Aided by this high-resolution, single-cell expression approach, we computationally identify colony-stimulating factor 1 receptor and cluster of differentiation 86 as targets for CAR-T cell therapy in AML. Functional validation of these established CAR-T cells shows robust in vitro and in vivo efficacy in cell line- and human-derived AML models with minimal off-target toxicity toward relevant healthy human tissues. This provides a strong rationale for further clinical development.
Identifiants
pubmed: 36914885
doi: 10.1038/s41587-023-01684-0
pii: 10.1038/s41587-023-01684-0
pmc: PMC7615296
mid: EMS163133
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1618-1632Subventions
Organisme : European Research Council
ID : 756017
Pays : International
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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