Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer
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Qiang Sun1, Shixin Zhou1, Jingjing Zhao1, Changwen Deng1, Ruidi Teng1, Yiding Zhao1, Jiajia Chen1, Jiebin Dong1, Ming Yin2, Yun Bai1, Hongkui Deng1,3,4 and Jinhua Wen1
1Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
2Beijing Vitalstar Biotechnology Co., Ltd., Beijing, China
3The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
4Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China
Jinhua Wen, email: [email protected]
Hongkui Deng, email: [email protected]
Yun Bai, email: [email protected]
Keywords: adoptive cell therapy; mesothelin; CAR; lung metastasis
Received: May 16, 2017 Accepted: November 13, 2017 Published: January 10, 2018
Pancreatic cancer is known as one of the most lethal cancers in the world. A majority of advanced stage pancreatic cancer patients are diagnosed with distant metastasis and given poor prognoses, calling for a better therapeutic option. Mesothelin, which is overexpressed in pancreatic cancer and other solid tumors, is a potential target for pancreatic cancer immunotherapy. Adoptive transfer of T cells engineered with chimeric antigen receptors (CART cells) was effective for treating CD19-positive leukemia, but it is more difficult for CART cells to eliminate solid tumors. Because distal metastasis is an important malignant behavior of solid tumors, we investigated whether meso-CART cells exert anti-tumor effects against distant metastases. After expressing meso-CAR in human primary T lymphocytes, the resultant meso-CART cells released cytokines in response to and exhibited cytolytic effects on mesothelin-positive tumor cells in vitro. Injection of meso-CART cells into tumor-bearing mice moderately delayed subcutaneous tumor growth and eliminated lung metastases. This is the first study to show that meso-CART cells are effective against lung metastases induced by intravenous injection of pancreatic tumor cells. Our results suggest that meso-CART cells may be an effective clinical treatment for mesothelin-positive primary and metastatic tumors in pancreatic cancer patients.
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