DLK1-directed chimeric antigen receptor T-cell therapy for hepatocellular carcinoma.
Liver Int
; 42(11): 2524-2537, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36002393
ABSTRACT
BACKGROUND:
Delta-like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1-directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1-positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy.METHODS:
We first characterized a homemade anti-human DLK1 monoclonal antibody, sequenced the single-chain Fragment variable (scFv) and integrated it into the second-generation CAR lentiviral vector, and then developed the DLK1-directed CAR-T cells. The cytotoxic activities of DLK1-directed CAR-T cells against different HCC cells were evaluated in vitro and in vivo.RESULTS:
The genetically modified human T cells with the DLK1-directed CARs produced cytotoxic activity against DLK1-positive HCC cells. Additionally, the DLK1-directed CARs enhanced T cell proliferation and activation in a DLK1-dependent manner. Interestingly, the DLK1-targeted CAR-T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh-7.CONCLUSION:
DLK1-directed CAR-T cells specifically suppresses DLK1-positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR-T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Receptores de Antígenos Quiméricos
/
Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China