Galunisertib enhances chimeric antigen receptor-modified T cell function
Wang, Zhixiong1,2,3; Liu, Qian1; Risu, Na3; Fu, Jiayu3; Zou, Yan4; Tang, Jiaxing4; Li, Long4; Liu, Hui1; Zhou, Guomin1; Zhu, Xuekai4
2020
Source PublicationEUROPEAN JOURNAL OF HISTOCHEMISTRY
ISSN1121-760X
EISSN2038-8306
Volume64Pages:#VALUE!
DOI10.4081/ejh.2020.3122
AbstractChimeric 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.
KeywordCAR T TGF-beta solid tumor immunotherapy immunosuppression
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Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000614541300001
PublisherPAGEPRESS PUBL
WOS KeywordTGF-BETA ; INHIBITION ; MECHANISMS ; EXPRESSION ; TGF-BETA-1 ; LY2157299
Original Document TypeArticle
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125998
Collection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
Affiliation1.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
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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!.
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