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

Heng Zhang; Hui Zhao; Xiaolei He; Feng Xi; Jiwen Liu

doi:10.2147/CMAR.S264358

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

Cancer Manag Res. 2020 Oct 8:12:9813-9824. doi: 10.2147/CMAR.S264358. eCollection 2020.

Authors

Heng Zhang¹, Hui Zhao², Xiaolei He³, Feng Xi⁴, Jiwen Liu¹

Affiliations

¹ School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People's Republic of China.
² Department of Radiation Therapy, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, Xinjiang Uygur Autonomous Region, People's Republic of China.
³ Department of Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People's Republic of China.
⁴ Medical Department, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, Xinjiang Uygur Autonomous Region, People's Republic of China.

Abstract

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

Grants and funding

This work was supported by Xinjiang Uygur Autonomous Region Natural Science Foundation Project (2019D01C108). The study design, workflow development, data analysis, interpretation, and writing are solely the responsibility of the authors; no members of the funding organizations participated in or influenced these activities.