Ligand‐Based <scp>CAR</scp>‐T Cells Targeting <scp>EGFR</scp> Exhibit Favorable Antitumor Effects Against Gynecologic Malignancies

Epidermal 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.