Light-Controllable Binary Switch Activation of CAR T Cells.
ChemMedChem
; 17(12): e202100722, 2022 06 20.
Article
em En
| MEDLINE
| ID: mdl-35146940
ABSTRACT
Major challenges to chimeric antigen receptor (CAR) T cell therapies include uncontrolled immune activity, off-tumor toxicities and tumor heterogeneity. To overcome these challenges, we engineered CARs directed against small molecules. By conjugating the same small molecule to distinct tumor-targeting antibodies, we show that small molecule specific-CAR T cells can be redirected to different tumor antigens. Such binary switches allow control over the degree of CAR T cell activity and enables simultaneous targeting of multiple tumor-associated antigens. We also demonstrate that ultraviolet light-sensitive caging of small molecules blocks CAR T cell activation. Exposure to ultraviolet light, uncaged small molecules and restored CAR T cell-mediated killing. Together, our data demonstrate that a light-sensitive caging system enables an additional level of control over tumor cell killing, which could improve the therapeutic index of CAR T cell therapies.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoterapia Adotiva
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article