Galunisertib enhances chimeric antigen receptor-modified T cell function
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 molecul...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
PAGEPress Publications
2020-06-01
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| Series: | European Journal of Histochemistry |
| Subjects: | |
| Online Access: | https://www.ejh.it/index.php/ejh/article/view/3122 |
| _version_ | 1811271377801445376 |
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| author | Zhixiong Wang Qian Liu Na Risu Jiayu Fu Yan Zou Jiaxing Tang Long Li Hui Liu Guomin Zhou Xuekai Zhu |
| author_facet | Zhixiong Wang Qian Liu Na Risu Jiayu Fu Yan Zou Jiaxing Tang Long Li Hui Liu Guomin Zhou Xuekai Zhu |
| author_sort | Zhixiong Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T22:20:05Z |
| format | Article |
| id | doaj.art-db521129388c4f289f67c8e15404cb10 |
| institution | Directory Open Access Journal |
| issn | 1121-760X 2038-8306 |
| language | English |
| last_indexed | 2024-04-12T22:20:05Z |
| publishDate | 2020-06-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj.art-db521129388c4f289f67c8e15404cb102022-12-22T03:14:24ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062020-06-0164s210.4081/ejh.2020.3122Galunisertib enhances chimeric antigen receptor-modified T cell functionZhixiong Wang0Qian Liu1Na Risu2Jiayu Fu3Yan Zou4Jiaxing Tang5Long Li6Hui Liu7Guomin Zhou8Xuekai ZhuSchool of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, ShanghaiSchool of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, ShanghaiDivision of Health Science, Graduate School of Medicine, Osaka University, OsakaDivision of Health Science, Graduate School of Medicine, Osaka University, OsakaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, ShanghaiShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, ShanghaiShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, ShanghaiShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, ShanghaiSchool of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, ShanghaiChimeric 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.https://www.ejh.it/index.php/ejh/article/view/3122CAR TTGF-βsolid tumorimmunotherapyimmunosuppression |
| spellingShingle | Zhixiong Wang Qian Liu Na Risu Jiayu Fu Yan Zou Jiaxing Tang Long Li Hui Liu Guomin Zhou Xuekai Zhu Galunisertib enhances chimeric antigen receptor-modified T cell function European Journal of Histochemistry CAR T TGF-β solid tumor immunotherapy immunosuppression |
| title | Galunisertib enhances chimeric antigen receptor-modified T cell function |
| title_full | Galunisertib enhances chimeric antigen receptor-modified T cell function |
| title_fullStr | Galunisertib enhances chimeric antigen receptor-modified T cell function |
| title_full_unstemmed | Galunisertib enhances chimeric antigen receptor-modified T cell function |
| title_short | Galunisertib enhances chimeric antigen receptor-modified T cell function |
| title_sort | galunisertib enhances chimeric antigen receptor modified t cell function |
| topic | CAR T TGF-β solid tumor immunotherapy immunosuppression |
| url | https://www.ejh.it/index.php/ejh/article/view/3122 |
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