Gastric cancer is the third leading cause of cancer-related mortalities worldwide and mostly incurable. It remains an urgent need for novel strategies in the management of patients with advanced gastric cancer. Chimeric antigen receptor (CAR) T therapy has shown unprecedented clinical success in hematological malignancies and potential utility is going on various solid tumors like gastric cancer. In this study, a broad expression of NKG2D ligands was observed in gastric cancer cell lines, making them suitable targets for gastric cancer therapy. T cells were engineered with an NKG2D-based second-generation CAR and the resulting NKG2D-CAR-T cells showed significantly increased cytolytic activity against gastric cancer compared to untransduced T cells. In vivo, these cells can significantly suppressed the growth of established gastric cancer xenografts. Besides, cisplatin was shown to upregulate NKG2D ligand expression in gastric cancer cells and enhance the susceptibility to NKG2D-CAR-T-cell-mediated cytotoxicity. In conclusion, NKG2D-based CAR-T cells have potent in vivo and in vitro anti-tumor activities against gastric cancer and could be a new paradigm for patients with gastric cancer, either used alone or combined with chemotherapy.
NKG2D Chimeric antigen receptor Gastric cancer
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LYQ conceived idea, designed research and revised the manuscript; TKL and HM designed subsequent experiments, performed most of the in vitro and in vivo work, and wrote the manuscript; TF and XGG helped perform the in vivo experiments; YMF and ZYY assisted with interpretation of data and helped to perform the in vitro and in vivo work.
Compliance with ethical standards
Conflict of interest
All other authors have no conflicts of interest to disclose.
Informed consent was obtained from all individual participants included in the study.
Research involving human participants
Written informed consent was obtained from each donor under a protocol approved by the Committee on Clinical investigation for the use of blood for cancer research.
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