Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
Li Mao, Sheng Su, Jia Li, Songyang Yu, Yu Gong, Changzhou Chen, Zhiqiang Hu, Xiaowu Huang
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a common malignancy arising from the liver with limited 5-year survival. Thus, there is an urgency to explore new treatment methods. Chimeric antigen receptor T (CAR T) cell therapy is a very promising cancer treatment. Though, several groups have investigated CAR T cells targeting MUC1 in solid cancer models, Tn-MUC1-targeted CAR T cells have not yet to be reported in ICC. In this study, we confirmed Tn-MUC1 as a potential therapeutic target for ICC and demonstrated that its expression level was positively correlated with the poor prognosis of ICC patients. More importantly, we successfully developed effective CAR T cells to target Tn-MUC1-positive ICC tumors and explored their antitumor activities. Our results suggest the CAR T cells could specifically eliminate Tn-MUC1-positive ICC cells, but not Tn-MUC1-negative ICC cells, in vitro and in vivo. Therefore, our study is expected to provide new therapeutic strategies and ideas for the treatment of ICC.