A modular and controllable T cell therapy platform for acute myeloid leukemia.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
17
06
2020
accepted:
01
12
2020
revised:
09
11
2020
pubmed:
9
1
2021
medline:
1
9
2021
entrez:
8
1
2021
Statut:
ppublish
Résumé
Targeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and where off-tumor on-target-associated toxicity is manageable. Although acute myeloid leukemia (AML) has in principle been shown to be a T cell-sensitive disease by the graft-versus-leukemia activity of allogeneic stem cell transplantation, T cell therapy has so far failed in this setting. This is largely due to the lack of target structures both sufficiently selective and uniformly expressed on AML, causing unacceptable myeloid cell toxicity. To address this, we developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to AML. This platform combines synthetic agonistic receptor (SAR) -transduced T cells with AML-targeting tandem single chain variable fragment (scFv) constructs. Construct exchange allows SAR T cells to be redirected toward alternative targets, a process enabled by the short half-life and controllability of these antibody fragments. Combining SAR-transduced T cells with the scFv constructs resulted in selective killing of CD33
Identifiants
pubmed: 33414484
doi: 10.1038/s41375-020-01109-w
pii: 10.1038/s41375-020-01109-w
pmc: PMC7789085
mid: EMS114666
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2243-2257Subventions
Organisme : European Research Council
ID : 756017
Pays : International
Informations de copyright
© 2021. The Author(s).
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