Galunisertib enhances chimeric antigen receptor-modified T cell function

Submitted: 16 March 2020
Accepted: 11 April 2020
Published: 19 June 2020
Abstract Views: 979
PDF: 674
Supplementary: 0
HTML: 10
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Chimeric antigen receptor (CAR) T cell therapy still faces the challenge of immunosuppression when treating solid tumors. TGF-β is one of the critical factors in the tumor microenvironment to help tumors escape surveillance by the immune system. Here we tried using the combination of a small molecule inhibitor of TGF-β receptor I, Galunisertib, and CAR T cells to explore whether Galunisertib could enhance CAR T cell function against solid tumor cells. In vitro experiments showed Galunisertib could significantly enhance the specific cytotoxicity of both CD133- and HER2-specific CAR T cells. However, Galunisertib had no direct killing effect on target cells. Galunisertib significantly increased the cytokine secretion of CAR T cells and T cells that do not express CAR (Nontransfected T cells). Galunisertib did not affect the proliferation of T cells, the antigen expression on target cells and CD69 on CAR T cells. We found that TGF-β was secreted by T cells themselves upon activation, and Galunisertib could reduce TGF-β signaling in CAR T cells. Our findings can provide the basis for further preclinical and clinical studies of the combination of Galunisertib and CAR T cells in the treatment of solid tumors.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Zhixiong Wang, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai

Ma’anshan University, Ma’anshan, China
Division of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan

How to Cite

Wang, Z., Liu, Q., Risu, N., Fu, J., Zou, Y., Tang, J., Li, L., Liu, H., Zhou, G., & Zhu, X. . (2020). Galunisertib enhances chimeric antigen receptor-modified T cell function. European Journal of Histochemistry, 64(s2). https://doi.org/10.4081/ejh.2020.3122