@article{Wang_Liu_Risu_Fu_Zou_Tang_Li_Liu_Zhou_Zhu_2020, title={Galunisertib enhances chimeric antigen receptor-modified T cell function}, volume={64}, url={https://www.ejh.it/ejh/article/view/3122}, DOI={10.4081/ejh.2020.3122}, abstractNote={<p>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. <em>In vitro</em> 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.</p>}, number={s2}, journal={European Journal of Histochemistry}, author={Wang, Zhixiong and Liu, Qian and Risu, Na and Fu, Jiayu and Zou, Yan and Tang, Jiaxing and Li, Long and Liu, Hui and Zhou, Guomin and Zhu, Xuekai}, year={2020}, month={Jun.} }