Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia
Background As a malignancy of hematopoietic origin, the standard-of-care cytoreductive chemotherapy can not provide satisfactory treatment effect for patients with acute myeloid leukemia (AML). Immunotherapy has received increasing attention in leukemia treatment. However, the immunosuppressive micr...
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BMJ Publishing Group
2025-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/7/e011148.full |
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| author | Jing Yang Ling Zhang Nan Wu Jiayuan Hu Jun Ren Xinyi Chen Xingyu Wei Minghui Sun Ziwei Li Yongcan Liu Yan Shu Genyou Li Fangfang Jin Can Lin Lisha Tang Zesong Yang |
| author_facet | Jing Yang Ling Zhang Nan Wu Jiayuan Hu Jun Ren Xinyi Chen Xingyu Wei Minghui Sun Ziwei Li Yongcan Liu Yan Shu Genyou Li Fangfang Jin Can Lin Lisha Tang Zesong Yang |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | Background As a malignancy of hematopoietic origin, the standard-of-care cytoreductive chemotherapy can not provide satisfactory treatment effect for patients with acute myeloid leukemia (AML). Immunotherapy has received increasing attention in leukemia treatment. However, the immunosuppressive microenvironment and low cancer immunogenicity of AML blasts create major obstacles to effectively inducing immune responses.Methods We developed an extracellular vesicle-based dual-delivery biosystem, which enhanced anti-AML immune responses by activating the immunogenicity of leukemia cells and relieving immunosuppression in AML allografted mice. Red blood cell-derived extracellular vesicles (REVs) were selected as delivery carriers due to the excellent biocompatibility. REVs were ligated with leukemia-targeting peptide P9 and subsequently loaded with immunogenic cell death (ICD) inducer (Doxorubicin, Dox) and indoleamine 2,3-dioxygenase-1 siRNA (siIDO1) to construct a chemoimmunological cascade biosystem (REVs-Dox/siIDO1-P9).Results The biosystem can specifically deliver the loaded Dox and siIDO1 into target leukemia cells and was validated capable of inducing efficient ICD. ICD-mediated release of damage-associated molecular patterns synergistically functions with siIDO1-mediated IDO1 silence to effectually recruit CD8+ T cells and enhance CD8+ T cell’s functions. In the AML mouse model, REVs-Dox/siIDO1-P9 can evoke a strong antileukemia response and prolong leukemia-bearing mice survival compared with REVs-Dox/siNC-P9 and REVs-siIDO1-P9.Conclusion Our findings indicate that the extracellular vesicle-based chemoimmunological cascade biosystem provides a novel strategy for AML treatment. |
| format | Article |
| id | doaj-art-e40e6c0bf6ed4b6bb45ea0d21f0b2c2d |
| institution | Matheson Library |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e40e6c0bf6ed4b6bb45ea0d21f0b2c2d2025-07-16T12:40:14ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-07-0113710.1136/jitc-2024-011148Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemiaJing Yang0Ling Zhang1Nan Wu2Jiayuan Hu3Jun Ren4Xinyi Chen5Xingyu Wei6Minghui Sun7Ziwei Li8Yongcan Liu9Yan Shu10Genyou Li11Fangfang Jin12Can Lin13Lisha Tang14Zesong Yang151 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China2 Department of Laboratory Medicine, Chongqing University Fuling Hospital, School of Medicine, Chongqing University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China2 Department of Laboratory Medicine, Chongqing University Fuling Hospital, School of Medicine, Chongqing University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China1 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China3 Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaBackground As a malignancy of hematopoietic origin, the standard-of-care cytoreductive chemotherapy can not provide satisfactory treatment effect for patients with acute myeloid leukemia (AML). Immunotherapy has received increasing attention in leukemia treatment. However, the immunosuppressive microenvironment and low cancer immunogenicity of AML blasts create major obstacles to effectively inducing immune responses.Methods We developed an extracellular vesicle-based dual-delivery biosystem, which enhanced anti-AML immune responses by activating the immunogenicity of leukemia cells and relieving immunosuppression in AML allografted mice. Red blood cell-derived extracellular vesicles (REVs) were selected as delivery carriers due to the excellent biocompatibility. REVs were ligated with leukemia-targeting peptide P9 and subsequently loaded with immunogenic cell death (ICD) inducer (Doxorubicin, Dox) and indoleamine 2,3-dioxygenase-1 siRNA (siIDO1) to construct a chemoimmunological cascade biosystem (REVs-Dox/siIDO1-P9).Results The biosystem can specifically deliver the loaded Dox and siIDO1 into target leukemia cells and was validated capable of inducing efficient ICD. ICD-mediated release of damage-associated molecular patterns synergistically functions with siIDO1-mediated IDO1 silence to effectually recruit CD8+ T cells and enhance CD8+ T cell’s functions. In the AML mouse model, REVs-Dox/siIDO1-P9 can evoke a strong antileukemia response and prolong leukemia-bearing mice survival compared with REVs-Dox/siNC-P9 and REVs-siIDO1-P9.Conclusion Our findings indicate that the extracellular vesicle-based chemoimmunological cascade biosystem provides a novel strategy for AML treatment.https://jitc.bmj.com/content/13/7/e011148.full |
| spellingShingle | Jing Yang Ling Zhang Nan Wu Jiayuan Hu Jun Ren Xinyi Chen Xingyu Wei Minghui Sun Ziwei Li Yongcan Liu Yan Shu Genyou Li Fangfang Jin Can Lin Lisha Tang Zesong Yang Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia Journal for ImmunoTherapy of Cancer |
| title | Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia |
| title_full | Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia |
| title_fullStr | Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia |
| title_full_unstemmed | Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia |
| title_short | Engineered red blood cell extracellular vesicles for delivery of Dox and siIDO1 enhance targeted chemo-immunotherapy of acute myeloid leukemia |
| title_sort | engineered red blood cell extracellular vesicles for delivery of dox and siido1 enhance targeted chemo immunotherapy of acute myeloid leukemia |
| url | https://jitc.bmj.com/content/13/7/e011148.full |
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