Galunisertib enhances chimeric antigen receptor-modified T cell function

European Journal of Histochemistry

XuekaiZhu¹  Na Risu²  Jiayu Fu²  Zhixiong Wang³  Guomin Zhou³  Qian Liu³  Long Li⁴  Yan Zou⁴  Jiaxing Tang⁴  Hui Liu⁴ 

[1] ;Division of Health Science, Graduate School of Medicine, Osaka University, Osaka;School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai;Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai;

关键词: CAR T;    TGF-β;    solid tumor;    immunotherapy;    immunosuppression;   

DOI  :  10.4081/ejh.2020.3122

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown