Antitumor activity of NKG2D CAR-T cells against human colorectal cancer cells in vitro and in vivo.

Colorectal cancer is one of the most common malignancies worldwide, as it is often diagnosed at an advanced stage. Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success and emerged as one of the most promising therapeutic strategies in multiple malignancies. The purpose of this study was to investigate the anti-tumor activity of NKG2D CAR-T cells against human colorectal cancer cells. A non-viral third-generation NKG2D CAR was constructed, and subsequently transduced into T cells to obtain the NKG2D CAR-T cells. In vitro, NKG2D CAR-T cells showed cytotoxicity against human colorectal cancer cells in a dose-dependent manner compared with untransduced T cells. In addition, IL-2 and IFN-γ secreted by these cells were significantly higher than those by untransduced T cells. In vivo, NKG2D CAR-T cells significantly suppressed tumor growth, reduced tumor sizes and extended overall survival of mice in a xenograft model of HCT-116 cells. Furthermore, human NKG2D-positive lymphocytes infiltration could be found in the tumor sections of NKG2D CAR-T cells-treated mice. There were no severe pathological changes found in vital organs in any of the treatment groups. NKG2D CAR-T cells showed excellent killing effect and represented a promising immunotherapeutic strategy against human colorectal cancer.