TY - JOUR AU - Wang, Zhixiong AU - Liu, Qian AU - Risu, Na AU - Fu, Jiayu AU - Zou, Yan AU - Tang, Jiaxing AU - Li, Long AU - Liu, Hui AU - Zhou, Guomin AU - Zhu, Xuekai PY - 2020/06/19 Y2 - 2024/03/19 TI - Galunisertib enhances chimeric antigen receptor-modified T cell function JF - European Journal of Histochemistry JA - Eur J Histochem VL - 64 IS - s2 SE - Special Issue - Stem cells and regenerative medicine DO - 10.4081/ejh.2020.3122 UR - https://www.ejh.it/ejh/article/view/3122 SP - AB - <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> ER -