TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy
Tumor necrosis factor–related apoptosis-inducing ligand receptor 1 (TRAIL-R1) has limited expression in normal tissues but was highly expressed in various types of tumors, making it an attractive target for cancer immunotherapy. Here, we utilized the single-chain variable fragment (scFv) from our pr...
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| Format: | Article |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.756599/full |
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| author | Yaru Nai Yaru Nai Li Du Li Du Meiying Shen Meiying Shen Tingting Li Tingting Li Jingjing Huang Jingjing Huang Xiaojian Han Xiaojian Han Feiyang Luo Feiyang Luo Wang Wang Wang Wang Da Pang Aishun Jin Aishun Jin |
| author_facet | Yaru Nai Yaru Nai Li Du Li Du Meiying Shen Meiying Shen Tingting Li Tingting Li Jingjing Huang Jingjing Huang Xiaojian Han Xiaojian Han Feiyang Luo Feiyang Luo Wang Wang Wang Wang Da Pang Aishun Jin Aishun Jin |
| author_sort | Yaru Nai |
| collection | DOAJ |
| description | Tumor necrosis factor–related apoptosis-inducing ligand receptor 1 (TRAIL-R1) has limited expression in normal tissues but was highly expressed in various types of tumors, making it an attractive target for cancer immunotherapy. Here, we utilized the single-chain variable fragment (scFv) from our previously identified TRAIL-R1–targeting monoclonal antibody (TR1419) with antitumor efficacy and produced the TR1419 chimeric antigen receptor (CAR) T cells. We characterized the phenotypes and functions of these CAR-T cells and found that the third-generation TR1419-28BBζ CAR-T cells exhibited greater target sensitivity and proliferative capability, with slightly higher PD-1 expression after antigen stimulation. Importantly, we found that the TR1419 CAR-T cells could induce TRAIL-R1–positive tumor cell death via a dual mechanism of the death receptor–dependent apoptosis as well as the T-cell–mediated cytotoxicity. Altogether, the TR1419 CAR-T cells could serve as a promising strategy for targeting the TRAIL-R1–positive tumors. |
| first_indexed | 2024-12-22T21:35:38Z |
| format | Article |
| id | doaj.art-e9137bce93c845b59b9fb3bd1224c490 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-22T21:35:38Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-e9137bce93c845b59b9fb3bd1224c4902022-12-21T18:11:47ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-12-01810.3389/fmolb.2021.756599756599TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor EfficacyYaru Nai0Yaru Nai1Li Du2Li Du3Meiying Shen4Meiying Shen5Tingting Li6Tingting Li7Jingjing Huang8Jingjing Huang9Xiaojian Han10Xiaojian Han11Feiyang Luo12Feiyang Luo13Wang Wang14Wang Wang15Da Pang16Aishun Jin17Aishun Jin18Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Endocrine Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaChongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, ChinaDepartment of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, ChinaTumor necrosis factor–related apoptosis-inducing ligand receptor 1 (TRAIL-R1) has limited expression in normal tissues but was highly expressed in various types of tumors, making it an attractive target for cancer immunotherapy. Here, we utilized the single-chain variable fragment (scFv) from our previously identified TRAIL-R1–targeting monoclonal antibody (TR1419) with antitumor efficacy and produced the TR1419 chimeric antigen receptor (CAR) T cells. We characterized the phenotypes and functions of these CAR-T cells and found that the third-generation TR1419-28BBζ CAR-T cells exhibited greater target sensitivity and proliferative capability, with slightly higher PD-1 expression after antigen stimulation. Importantly, we found that the TR1419 CAR-T cells could induce TRAIL-R1–positive tumor cell death via a dual mechanism of the death receptor–dependent apoptosis as well as the T-cell–mediated cytotoxicity. Altogether, the TR1419 CAR-T cells could serve as a promising strategy for targeting the TRAIL-R1–positive tumors.https://www.frontiersin.org/articles/10.3389/fmolb.2021.756599/fullTRAIL-R1CAR-Tapoptosiscytotoxicitythird generation |
| spellingShingle | Yaru Nai Yaru Nai Li Du Li Du Meiying Shen Meiying Shen Tingting Li Tingting Li Jingjing Huang Jingjing Huang Xiaojian Han Xiaojian Han Feiyang Luo Feiyang Luo Wang Wang Wang Wang Da Pang Aishun Jin Aishun Jin TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy Frontiers in Molecular Biosciences TRAIL-R1 CAR-T apoptosis cytotoxicity third generation |
| title | TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy |
| title_full | TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy |
| title_fullStr | TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy |
| title_full_unstemmed | TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy |
| title_short | TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy |
| title_sort | trail r1 targeted car t cells exhibit dual antitumor efficacy |
| topic | TRAIL-R1 CAR-T apoptosis cytotoxicity third generation |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.756599/full |
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