Galunisertib enhances chimeric antigen receptor-modified T cell function

doi:10.4081/ejh.2020.3122

	Galunisertib enhances chimeric antigen receptor-modified T cell function
	Wang, Zhixiong 1,2,3; Liu, Qian 1; Risu, Na 3; Fu, Jiayu 3; Zou, Yan4 ; Tang, Jiaxing4 ; Li, Long4 ; Liu, Hui 1; Zhou, Guomin 1; Zhu, Xuekai4
	2020
发表期刊	EUROPEAN JOURNAL OF HISTOCHEMISTRY (IF:2.1[JCR-2023],2.0[5-Year])
ISSN	1121-760X
EISSN	2038-8306
卷号	64 页码:#VALUE!
DOI	10.4081/ejh.2020.3122
摘要	Chimeric antigen receptor (CAR) T cell therapy still faces the challenge of immunosuppression when treating solid tumors. TGF-beta 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-beta 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-beta was secreted by T cells themselves upon activation, and Galunisertib could reduce TGF-beta 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.
关键词	CAR T TGF-beta solid tumor immunotherapy immunosuppression
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收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000614541300001
出版者	PAGEPRESS PUBL
WOS关键词	TGF-BETA ; INHIBITION ; MECHANISMS ; EXPRESSION ; TGF-BETA-1 ; LY2157299
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125998
专题	免疫化学研究所_PI研究组_刘佳组免疫化学研究所_PI研究组_朱学锴组 T细胞工程实验室免疫化学研究所_特聘教授组_蒋华良组生命科学与技术学院_博士生
通讯作者	Zhu, Xuekai
作者单位	1.Univ Shanghai Sci & Technol, Sch Med Instrument & Food Engn, Shanghai, Peoples R China; 2.Maanshan Univ, Maanshan, Peoples R China; 3.Osaka Univ, Grad Sch Med, Div Hlth Sci, Osaka, Japan; 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies SIAIS, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Wang, Zhixiong,Liu, Qian,Risu, Na,et al. Galunisertib enhances chimeric antigen receptor-modified T cell function[J]. EUROPEAN JOURNAL OF HISTOCHEMISTRY,2020,64:#VALUE!.
APA	Wang, Zhixiong.,Liu, Qian.,Risu, Na.,Fu, Jiayu.,Zou, Yan.,...&Zhu, Xuekai.(2020).Galunisertib enhances chimeric antigen receptor-modified T cell function.EUROPEAN JOURNAL OF HISTOCHEMISTRY,64,#VALUE!.
MLA	Wang, Zhixiong,et al."Galunisertib enhances chimeric antigen receptor-modified T cell function".EUROPEAN JOURNAL OF HISTOCHEMISTRY 64(2020):#VALUE!.