Koichi Hirabayashi

Ligand‐Based CAR‐T Cells Targeting EGFR Exhibit Favorable Antitumor Effects Against Gynecologic Malignancies

ABSTRACTEpidermal growth factor receptor (EGFR) has been reported to be overexpressed in gynecologic malignancies. However, the clinical efficacy of existing molecular EGFR‐targeted therapies against gynecologic malignancies has not been demonstrated. In this study, we investigated the antitumor effects of ligand‐based EGFR chimeric antigen receptor (CAR)‐T cells on gynecologic malignancies. First, we evaluated EGFR expression in patient samples using immunohistochemistry. EGFR positivity was observed in 41%, 82%, and 79% of ovarian, endometrial, and cervical cancer in patient samples, respectively. Second, we generated ligand‐based EGFR CAR‐T cells via piggyBac‐mediated gene transfer. EGFR CAR‐T cells were successfully generated with high CAR positivity and a high proportion of naïve/stem cell memory‐like T cells. Finally, we investigated the antitumor effects of EGFR CAR‐T cells on gynecologic malignancies. EGFR CAR‐T cells were co‐cultured with six EGFR‐positive gynecologic cancer cell lines. The growth of all six gynecologic cancer cell lines was significantly suppressed by EGFR CAR‐T cells compared to mock T cells. In in vivo studies, tumor‐bearing mice implanted with gynecologic cancer cell lines in their intraperitoneal cavity were administered EGFR CAR‐T cells, CD19 CAR‐T cells, or PBS intraperitoneally. Mice treated with EGFR CAR‐T cells displayed a significantly decreased tumor burden compared to those treated with either CD19 CAR‐T cells or PBS. Additionally, mice treated with EGFR CAR‐T cells had a significantly longer survival than the other groups. In summary, ligand‐based EGFR CAR‐T cells may be a promising therapy for various gynecologic malignancies.