Targeting and suppression of HER3-positive breast cancer by T lymphocytes expressing a heregulin chimeric antigen receptor.
Cancer Immunol Immunother
; 67(3): 393-401, 2018 03.
Article
en En
| MEDLINE
| ID: mdl-29127433
ABSTRACT
Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1ß (HRG1ß) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors. Our results showed that HRG1ß-CAR was successfully constructed, and T cells were transduced at a rate of 50%. The CAR-T cells specifically recognized and killed HER3-overexpressing breast cancer cells SK-BR-3 and BT-474 in vitro, and displayed potent tumoricidal effect on SK-BR-3 xenograft tumor models. Our results suggest that HRG1ß-based CAR-T cells effectively suppress breast cancer driven by HER family receptors, and may provide a novel strategy to overcome cancer resistance to HER2-targeted therapy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Linfocitos T
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Linfocitos T Citotóxicos
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Receptor ErbB-3
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Neurregulina-1
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Tratamiento Basado en Trasplante de Células y Tejidos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article