T cell receptor ß-chain-targeting chimeric antigen receptor T cells against T cell malignancies.
Nat Commun
; 13(1): 4334, 2022 07 26.
Article
en En
| MEDLINE
| ID: mdl-35882880
ABSTRACT
The success of chimeric antigen receptor (CAR) T cells in treating B cell malignancies comes at the price of eradicating normal B cells. Even though T cell malignancies are aggressive and treatment options are limited, similar strategies for T cell malignancies are constrained by the severe immune suppression arising from bystander T cell aplasia. Here, we show the selective killing of malignant T cells without affecting normal T cell-mediated immune responses in vitro and in a mouse model of disseminated leukemia. Further, we develop a CAR construct that carries the single chain variable fragment of a subtype-specific antibody against the variable TCR ß-chain region. We demonstrate that these anti-Vß8 CAR-T cells are able to recognize and kill all Vß8+ malignant T cells that arise from clonal expansion while sparing malignant or healthy Vß8- T cells, allowing sufficient T cell-mediated cellular immunity. In summary, we present a proof of concept for a selective CAR-T cell therapy to eradicate T cell malignancies while maintaining functional adaptive immunity, which opens the possibility for clinical development.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Quiméricos de Antígenos
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China