CELL INTELLIGENCE · 肿瘤细胞治疗研究

Pancreatic cancer is an aggressive malignancy with poor prognosis. Recent advances in chimeric antigen receptor (CAR)-T cell immunotherapy have offered renewed hope. The pivotal factors determining the effectiveness of CAR-T cells in the clinic is the selection of a reliable target and a specific ectodomain of CAR molecule. EpCAM is widely expressed in epithelial tumors, including pancreatic cancer, and is used as a tumor target in clinical trials of CAR-T cell therapy for gastric and colorectal cancers. However, the feasibility of using EpCAM CAR-T cells in pancreatic cancer still needs to be verified. In this work, we reported novel EpCAM CAR-T cells with a fully human single-chain variable fragment and evaluated their cytotoxic effects in a panel of pancreatic adenocarcinoma cell lines, three-dimensional tumor spheroid models and patient-derived organoids, and two xenograft mouse models. We demonstrated that EpCAM CAR-T cells exhibited potent and specific anti-tumor activity against EpCAM positive pancreatic cancer in vitro and in vivo, without adverse effects by systematic delivery in xenograft mouse models. Our preclinical results provided evidence of the efficacy and feasibility of EpCAM CAR-T cells for the immunotherapy of pancreatic cancer.