Cancer Management and Research (Oct 2020)
JAK-STAT Domain Enhanced MUC1-CAR-T Cells Induced Esophageal Cancer Elimination
Abstract
Heng Zhang,1 Hui Zhao,2 Xiaolei He,3 Feng Xi,4 Jiwen Liu1 1School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China; 2Department of Radiation Therapy, Xinjiang Uygur Autonomous Region People’s Hospital, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China; 3Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China; 4Medical Department, Xinjiang Uygur Autonomous Region People’s Hospital, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of ChinaCorrespondence: Jiwen LiuSchool of Public Health, Xinjiang Medical University, No. 393, Xinyi Road, Xincheng District, Urumqi, Xinjiang Uygur Autonomous Region 830011, People’s Republic of ChinaEmail [email protected]: Chimeric antigen receptor (CAR)-T cells have shown to play a vital role in anti-tumor functions in hematological malignancies, but have poor efficacy in solid tumors. To improve the activation and proliferation of CAR-T cell in solid tumors, we constructed an enhanced CAR-T cells to increase the survival of esophageal cancer.Materials and Methods: To construct enhanced CAR-T cells, we chose MUC1 as the target of CAR-T cells. Long-term co-culture of target cells and effector cells was applied to verify the antitumor activity of these enhanced MUC1-CAR-T cells in vitro. Moreover, a mouse xenograft model was established to investigate the effects of enhanced MUC1-CAR-T cells on tumor elimination in vivo.Results: In vitro studies showed that enhanced MUC1-CAR-T cells have long-lasting tumor killing and proliferative capabilities. Moreover, animal experiments verified that enhanced MUC1-CAR-T cells had significant antitumor function and a prolonged half-life by subcutaneous transplantation models of esophageal cancer and PDX models of esophageal cancer, in vivo.Conclusion: These results indicated that enhanced MUC1-CAR-T cells have a significant cytotoxic effect on esophageal cancer, and may likely to provide a novel strategy for the treatment of esophageal cancer.Keywords: JAK-STAT, MUC1, esophageal cancer, chimeric antigen receptor-T cells, CAR-T cell