期刊
TRANSLATIONAL ONCOLOGY
卷 39, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2023.101803
关键词
csGRP78; Gemcitabine; Pancreatic cancer; CAR-T
类别
This study demonstrates that csGRP78-directed CAR-T cells can selectively kill pancreatic cancer cells, and the combination with chemotherapy enhances cytotoxicity.
Pancreatic cancer is a highly lethal solid malignancy with limited treatment options. Chimeric antigen receptor T (CAR-T) cell therapy has been successfully applied to treat hematological malignancies, but faces many challenges in solid tumors. One major challenge is the shortage of tumor-selective targets. Cell surface GRP78 (csGRP78) is highly expressed on various solid cancer cells including pancreatic cancer, but not normal cells, providing a potential target for CAR-T cell therapy in pancreatic cancer. Here, we demonstrated that csGRP78directed CAR-T (GRP78-CAR-T) cells effectively killed the human pancreatic cancer cell lines Bxpc-3-luc, Aspc-1luc and MIA PaCa-2-luc, and pancreatic cancer stem-like cells derived from Aspc-1-luc cells and MIA PaCa-2-luc cells in vitro by a luciferase-based cytotoxicity assay. Importantly, we showed that GRP78-CAR-T cells efficiently homed to and infiltrated Aspc-1-luc cell-derived xenografts and significantly inhibited pancreatic tumor growth in vivo by performing mouse xenograft experiments. Interestingly, we found that gemcitabine treatment increased csGRP78 expression in gemcitabine-resistant MIA PaCa-2-luc cells, and the coapplication of gemcitabine with GRP78-CAR-T cells led to a robust cytotoxic effect on these cells in vitro. Taken together, our study demonstrates that csGRP78-directed CAR-T cells, alone or in combination with chemotherapy, selectively and efficiently target csGRP78-expressing pancreatic cancer cells to suppress pancreatic tumor growth.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据