Targeting and suppression of HER3-positive breast cancer by T lymphocytes expressing a heregulin chimeric antigen receptor

In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1 β (HRG1β) 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 HRG1β-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 HRG1β-based CAR-T cells effectively suppress breast cancer driven by HER family recepto rs, and may provide a novel strategy to overcome cancer resistance to HER2-targeted therapy.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research