Cancer Management and Research (Oct 2020)

JAK-STAT Domain Enhanced MUC1-CAR-T Cells Induced Esophageal Cancer Elimination

  • Zhang H,
  • Zhao H,
  • He X,
  • Xi F,
  • Liu J

Journal volume & issue
Vol. Volume 12
pp. 9813 – 9824

Abstract

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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

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