EGFR-specific CAR-T cells trigger cell lysis in EGFR-positive TNBC

Abstract

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are lacking. Epidermal growth factor receptor (EGFR) is overexpressed in various types of TNBC cells, and several EGFR-specific immunotherapies have been used to treat cancer patients. Chimeric antigen receptor engineered T (CAR-T) cells have also been used as cancer therapies. In this study, we generated two types of EGFR-specific CAR-modified T cells using lentiviral vectors with DNA sequences encoding the scFv regions of two anti-EGFR antibodies. The cytotoxic and antitumor effects of these CAR-modified T cells were examined in cytokine release and cytotoxicity assays in vitro and in tumor growth assays in TNBC cell line- and patient-derived xenograft mouse models. Both types of EGFR-specific CAR-T cells were activated by high-EGFR-expressing TNBC cells and specifically triggered TNBC cell lysis in vitro. Additionally, the CAR-T cells inhibited growth of cell-line- and patient-derived xenograft TNBC tumors in mice. These results suggest that EGFR-specific CAR-T cells might be a promising therapeutic strategy in patients with high-EGFR-expressing TNBC.

EGFR‐targeted CAR‐T cells are potent and specific in suppressing triple‐negative breast cancer both in vitro and in vivo

“…Consistently with what we observed in vitro , EGFR CAR‐T cell treatment at three different dosages was capable of suppressing TNBC growth/metastasis in xenograft mouse models. A recent study reported that the third generation of EGFR CAR‐T cells effectively suppressed TNBC cell growth in vitro and tumorigenesis in vivo in models including TNBC patient‐derived xenografts 76 . We observed that a medium dose of CAR‐T cell treatment exhibited the best in vivo effect, which might be because of an optimal number of injected CAR‐T cells and amount of released cytokines.…”

Emerging CAR-T Cell Therapy for the Treatment of Triple-Negative Breast Cancer

“…EGFR is a receptor tyrosine kinase that mediates oncogenic signaling cascades which drive the growth, survival, and invasion of cancer cells (79). Approximately 45% -70% of TNBC patients overexpress EGFR and efforts to target this receptor in TNBC are well underway (74)…”

Intercellular Adhesion Molecule-1 as Target for CAR-T-Cell Therapy of Triple-Negative Breast Cancer

“…Chimeric antigen receptors (CARs) are synthetic receptors that when engineered into T cells can redirect them to tumor cell surface antigens, get activated to become cytolytic, and eventually eliminate targeted tumor cells (9,10). Various CARs can be generated by fusing the antigen-specific variable singlechain fragments with T cell activating and co-stimulatory signaling domains (11,12). Chimeric antigen receptor T (CAR-T) immunotherapy is an effective immunotherapy strategy and plays an important role in cancer treatment.…”