Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer

Qiang Sun, Shixin Zhou, Jingjing Zhao, Changwen Deng, Ruidi Teng, Yiding Zhao, Jiajia Chen, Jiebin Dong, Ming Yin, Yun Bai, Hongkui Deng, Jinhua Wen
2018 OncoTarget  
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
more » ... 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.
doi:10.18632/oncotarget.24122 pmid:29568387 pmcid:PMC5862608 fatcat:sdssoetbsfhk5mdtb44dccffxe