mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia
Abstract Clinical trials of Chimeric Antigen Receptor T‐cell (CAR‐T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen‐targeting domains for CARs, owing to their high specificity, robust stabi...
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Wiley
2024-09-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202400024 |
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| author | Zhixiong Zhu Hexian Li Qizhong Lu Zongliang Zhang Jia Li Zeng Wang Nian Yang Zhengyu Yu Chen Yang Yongdong Chen Huaqing Lu Wei Wang Ting Niu Chunlai Nie Aiping Tong |
| author_facet | Zhixiong Zhu Hexian Li Qizhong Lu Zongliang Zhang Jia Li Zeng Wang Nian Yang Zhengyu Yu Chen Yang Yongdong Chen Huaqing Lu Wei Wang Ting Niu Chunlai Nie Aiping Tong |
| author_sort | Zhixiong Zhu |
| collection | DOAJ |
| description | Abstract Clinical trials of Chimeric Antigen Receptor T‐cell (CAR‐T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen‐targeting domains for CARs, owing to their high specificity, robust stability, and strong affinity, leading to significant advancements in the field of Nb‐CAR‐T. In the realm of T‐cell acute lymphoblastic leukemia (T‐ALL) targets, CD5 stands out as a potentially excellent candidate for T‐cell‐based CAR therapy, due to its distinct expression on the surface of malignant T‐ALL cells. To mitigate graft‐versus‐host disease associated with allogeneic CAR‐T, γδT cells are selected and stimulated from peripheral blood mononuclear cells, and γδT cells are engineered via CRISPR/Cas9 to eliminate fratricide, enabling the creation of fratricide‐resistant CAR‐γδTCD5− cells. In vitro transcribed (IVT) mRNA is used to construct CAR‐T, presenting a safer, faster, and cost‐effective method compared to traditional viral vector approaches. In this study, a CD5‐VHH library is constructed, and specific CD5‐nanobodies are screened for subsequent use in CD5‐CAR‐γδTCD5− therapy. IVT‐mRNA‐CD5‐CAR‐γδTCD5− cells exhibited favorable functional characteristics and demonstrated antitumor efficacy against malignant T cell lines, underlining the potential for advancing mRNA‐CD5‐CAR‐γδTCD5− therapy. |
| format | Article |
| id | doaj-art-8b15ce605dcc484b9a66e75fbf9aa14f |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-8b15ce605dcc484b9a66e75fbf9aa14f2025-08-20T01:55:16ZengWileyAdvanced Science2198-38442024-09-011135n/an/a10.1002/advs.202400024mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic LeukemiaZhixiong Zhu0Hexian Li1Qizhong Lu2Zongliang Zhang3Jia Li4Zeng Wang5Nian Yang6Zhengyu Yu7Chen Yang8Yongdong Chen9Huaqing Lu10Wei Wang11Ting Niu12Chunlai Nie13Aiping Tong14State Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaDepartment of Hematology State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaDepartment of Hematology State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaState Key Laboratory of Biotherapy and Cancer Center Collaborative Innovation Center of Biotherapy West China Hospital Sichuan University Chengdu 610041 ChinaAbstract Clinical trials of Chimeric Antigen Receptor T‐cell (CAR‐T) therapy have demonstrated remarkable success in treating both solid tumors and hematological malignancies. Nanobodies (Nbs) have emerged as promising antigen‐targeting domains for CARs, owing to their high specificity, robust stability, and strong affinity, leading to significant advancements in the field of Nb‐CAR‐T. In the realm of T‐cell acute lymphoblastic leukemia (T‐ALL) targets, CD5 stands out as a potentially excellent candidate for T‐cell‐based CAR therapy, due to its distinct expression on the surface of malignant T‐ALL cells. To mitigate graft‐versus‐host disease associated with allogeneic CAR‐T, γδT cells are selected and stimulated from peripheral blood mononuclear cells, and γδT cells are engineered via CRISPR/Cas9 to eliminate fratricide, enabling the creation of fratricide‐resistant CAR‐γδTCD5− cells. In vitro transcribed (IVT) mRNA is used to construct CAR‐T, presenting a safer, faster, and cost‐effective method compared to traditional viral vector approaches. In this study, a CD5‐VHH library is constructed, and specific CD5‐nanobodies are screened for subsequent use in CD5‐CAR‐γδTCD5− therapy. IVT‐mRNA‐CD5‐CAR‐γδTCD5− cells exhibited favorable functional characteristics and demonstrated antitumor efficacy against malignant T cell lines, underlining the potential for advancing mRNA‐CD5‐CAR‐γδTCD5− therapy.https://doi.org/10.1002/advs.202400024CAR‐TIVT‐mRNAT‐ALLγδT cells |
| spellingShingle | Zhixiong Zhu Hexian Li Qizhong Lu Zongliang Zhang Jia Li Zeng Wang Nian Yang Zhengyu Yu Chen Yang Yongdong Chen Huaqing Lu Wei Wang Ting Niu Chunlai Nie Aiping Tong mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia Advanced Science CAR‐T IVT‐mRNA T‐ALL γδT cells |
| title | mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia |
| title_full | mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia |
| title_fullStr | mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia |
| title_full_unstemmed | mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia |
| title_short | mRNA‐Engineered CD5‐CAR‐γδTCD5‐ Cells for the Immunotherapy of T‐Cell Acute Lymphoblastic Leukemia |
| title_sort | mrna engineered cd5 car γδtcd5 cells for the immunotherapy of t cell acute lymphoblastic leukemia |
| topic | CAR‐T IVT‐mRNA T‐ALL γδT cells |
| url | https://doi.org/10.1002/advs.202400024 |
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