T-ALL Cells as Tool Cells for CAR T Therapy
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in T...
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MDPI AG
2023-04-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/4/854 |
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| author | Anqi Ren Yuan Zhao Haichuan Zhu |
| author_facet | Anqi Ren Yuan Zhao Haichuan Zhu |
| author_sort | Anqi Ren |
| collection | DOAJ |
| description | T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in T cell malignancies, especially in T-ALL. The main reason for CAR T therapy limitations is that T-ALL cells and normal T cells share antigens, which improves the difficulty of sorting pure T cells, resulting in product contamination, and would lead to CAR T cell fratricide. Thus, we considered creating a CAR on T-ALL tumor cells (CAR T-ALL) to prevent fratricide and eliminate tumor cells. We found that T-ALL cells transduced with CAR would actually commit fratricide. However, CAR T-ALL could kill only tumor cells on T-ALL cell lines, and other types of tumor cells had no killing function after being transferred with CAR. Furthermore, we created CD99 CAR with expression controlled by the Tet-On system on Jurkat cells, which could avoid the fratricide of CAR T-ALL during proliferation, ensuring the controllability of the killing time and effect. Jurkat transduced with a CAR-targeting antigen, which was expressed on other cancer cells, could kill other cancer cell lines, demonstrating that T-ALL cells could be used as tool cells for cancer therapy. Our study supplied a new feasible treatment regimen for cancer treatment in the clinic. |
| first_indexed | 2024-03-11T04:27:08Z |
| format | Article |
| id | doaj.art-63af17c0961f4df882a24bb8a44d4c6d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T04:27:08Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-63af17c0961f4df882a24bb8a44d4c6d2023-11-17T21:42:42ZengMDPI AGVaccines2076-393X2023-04-0111485410.3390/vaccines11040854T-ALL Cells as Tool Cells for CAR T TherapyAnqi Ren0Yuan Zhao1Haichuan Zhu2Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, ChinaInstitute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, ChinaInstitute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, ChinaT-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in T cell malignancies, especially in T-ALL. The main reason for CAR T therapy limitations is that T-ALL cells and normal T cells share antigens, which improves the difficulty of sorting pure T cells, resulting in product contamination, and would lead to CAR T cell fratricide. Thus, we considered creating a CAR on T-ALL tumor cells (CAR T-ALL) to prevent fratricide and eliminate tumor cells. We found that T-ALL cells transduced with CAR would actually commit fratricide. However, CAR T-ALL could kill only tumor cells on T-ALL cell lines, and other types of tumor cells had no killing function after being transferred with CAR. Furthermore, we created CD99 CAR with expression controlled by the Tet-On system on Jurkat cells, which could avoid the fratricide of CAR T-ALL during proliferation, ensuring the controllability of the killing time and effect. Jurkat transduced with a CAR-targeting antigen, which was expressed on other cancer cells, could kill other cancer cell lines, demonstrating that T-ALL cells could be used as tool cells for cancer therapy. Our study supplied a new feasible treatment regimen for cancer treatment in the clinic.https://www.mdpi.com/2076-393X/11/4/854immunotherapiesT-cell acute lymphoblastic leukemiaCAR TCAR Jurkat |
| spellingShingle | Anqi Ren Yuan Zhao Haichuan Zhu T-ALL Cells as Tool Cells for CAR T Therapy Vaccines immunotherapies T-cell acute lymphoblastic leukemia CAR T CAR Jurkat |
| title | T-ALL Cells as Tool Cells for CAR T Therapy |
| title_full | T-ALL Cells as Tool Cells for CAR T Therapy |
| title_fullStr | T-ALL Cells as Tool Cells for CAR T Therapy |
| title_full_unstemmed | T-ALL Cells as Tool Cells for CAR T Therapy |
| title_short | T-ALL Cells as Tool Cells for CAR T Therapy |
| title_sort | t all cells as tool cells for car t therapy |
| topic | immunotherapies T-cell acute lymphoblastic leukemia CAR T CAR Jurkat |
| url | https://www.mdpi.com/2076-393X/11/4/854 |
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