A novel AXL chimeric antigen receptor endows T cells with anti-tumor effects against triple negative breast cancers
2018
Abstract Identifying targets for
chimeric antigen receptor-modulated T lymphocyte (CAR-T) therapy against solid tumors is an urgent problem to solve. In this study, we showed for the first time that the
receptor tyrosine kinase,
AXL, is overexpressed in various tumor cell lines and patient tumor tissues including
triple negative breast cancer(TNBC) cell lines and patient samples, making
AXLa potent novel target for cancer therapy, specifically for TNBC treatment. We also engineered T cells with a CAR consisting of a novel
single-chain variable fragmentagainst
AXLand revealed its antigen-specific cytotoxicity and ability to release cytokines in a TNBC cell line and other
AXL-positive tumors in vitro . Furthermore,
AXL-CAR-T cells displayed a significant anti-tumor effect and in vivo persistence in a TNBC xenograft model. Taken together, our findings indicate that
AXL-CAR-T cells can represent a promising therapeutic strategy against TNBC.
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