Role of Epidermal Growth Factor Receptor-Specific CAR-T Cells in the Suppression of Esophageal Squamous Cell Carcinoma.

Simple Summary: Esophageal squamous cell carcinoma (ESCC) is a high-incidence cancer in China for which treatment strategies and therapeutic effects are limited. In this study, we established cellular immunotherapy for ESCC using epidermal growth factor receptor (EGFR)-targeting chimeric antigen receptor (CAR)-expressing T cells. The goal of this project was to provide new and effective therapies for ESCC. ESCC is a highly malignant tumor, and its morbidity and mortality in China account for more than 50% of the world's total rates. As effective treatments are lacking, the 5-year survival rate of patients does not exceed 30%. CAR-T-cell-based immunotherapy has emerged as one of the most promising cancer treatments; however, there are relatively fewer reports regarding its application for ESCC. In this study, we conducted large-sample whole-genome sequencing (WGS) and RNA-seq analysis of patients with ESCC from China to examine the feasibility of EGFR-targeting CAR-T cells in the treatment of ESCC. We found much higher levels of EGFR gene amplification and overexpression in tumors than in the normal tissues, indicating that EGFR could be a promising target of CAR-T-cell-based immunotherapy in ESCC. Therefore, we tested EGFR-targeting CAR-T cells for lytic activity against ESCC cells as a model to establish cellular immunotherapy for ESCC. Five types of CAR-T cells targeting EGFR were constructed, two of which, CAR1-T and CAR2-T, showed a strong cytotoxicity against ESCC in in vitro and in vivo experiments. The results of this study suggest that CAR1-T and CAR2-T have the potential to be used for anti-ESCC immunotherapy in clinics. [ABSTRACT FROM AUTHOR]