4.5 Article

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

Journal

CANCER MANAGEMENT AND RESEARCH
Volume 12, Issue -, Pages 9813-9824

Publisher

DOVE MEDICAL PRESS LTD
DOI: 10.2147/CMAR.S264358

Keywords

JAK-STAT; MUC1; esophageal cancer; chimeric antigen receptor-T cells; CAR-T cell

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Funding

  1. Xinjiang Uygur Autonomous Region Natural Science Foundation Project [2019D01C108]

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Purpose: Chimeric antigen receptor (CAR)-T cells have shown to play a vital role in antitumor 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 MUC1CAR-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.

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