iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia
Abstract CD226 plays a vital role in NK cell cytotoxicity, interacting with its ligands on tumor targets. Acute myeloid leukemia (AML) cells have developed mechanisms to escape NK cell cytotoxicity, including inducing downregulation of CD226 on NK cells. Induced pluripotent stem cell -derived NK (iP...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-025-00686-9 |
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| author | Runze Cai Binyan Lu Xiangyu Zhao Shixin Zhou Yang Li |
| author_facet | Runze Cai Binyan Lu Xiangyu Zhao Shixin Zhou Yang Li |
| author_sort | Runze Cai |
| collection | DOAJ |
| description | Abstract CD226 plays a vital role in NK cell cytotoxicity, interacting with its ligands on tumor targets. Acute myeloid leukemia (AML) cells have developed mechanisms to escape NK cell cytotoxicity, including inducing downregulation of CD226 on NK cells. Induced pluripotent stem cell -derived NK (iPSC-NK) cells offer an important source of standardized off-the-shelf NK cell therapy to treat AML patients. In this study, we engineered iPSC-NK cells with CD226 to assess the ability of killing AML cells. iPSC-NK cells engineered with CD226 have a typical NK cell phenotype and demonstrate improved anti-AML activity and multiple cytokines releasing at low effector-to-target ratios. Transcriptomic analysis revealed upregulation of immune effector function pathways associated with cytotoxicity and immune activation in CD226-overexpression iPSC-NK cells. In an AML xenograft model, mice treated with CD226 overexpression iPSC-NK cells exhibited significantly reduced leukemia burden, prolonged survival, decreased systemic inflammation compared to those treated with Control iPSC-NK cells. Overall, our study provided evidence that iPSC derived-NK cells engineered with CD226 represent a promising candidate for off-the-shelf immunotherapy, particularly in AML and other CD226 ligand-expressing malignancies. |
| format | Article |
| id | doaj-art-eab8238d64c94d04a80ab8a67d817b49 |
| institution | Kabale University |
| issn | 2162-3619 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj-art-eab8238d64c94d04a80ab8a67d817b492025-08-20T03:46:00ZengBMCExperimental Hematology & Oncology2162-36192025-07-011411510.1186/s40164-025-00686-9iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemiaRunze Cai0Binyan Lu1Xiangyu Zhao2Shixin Zhou3Yang Li4Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking UniversityGuangzhou Regenverse Therapeutics Co.,LtdPeking University Institute of Hematology, Peking University People’s HospitalDepartment of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking UniversityDepartment of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking UniversityAbstract CD226 plays a vital role in NK cell cytotoxicity, interacting with its ligands on tumor targets. Acute myeloid leukemia (AML) cells have developed mechanisms to escape NK cell cytotoxicity, including inducing downregulation of CD226 on NK cells. Induced pluripotent stem cell -derived NK (iPSC-NK) cells offer an important source of standardized off-the-shelf NK cell therapy to treat AML patients. In this study, we engineered iPSC-NK cells with CD226 to assess the ability of killing AML cells. iPSC-NK cells engineered with CD226 have a typical NK cell phenotype and demonstrate improved anti-AML activity and multiple cytokines releasing at low effector-to-target ratios. Transcriptomic analysis revealed upregulation of immune effector function pathways associated with cytotoxicity and immune activation in CD226-overexpression iPSC-NK cells. In an AML xenograft model, mice treated with CD226 overexpression iPSC-NK cells exhibited significantly reduced leukemia burden, prolonged survival, decreased systemic inflammation compared to those treated with Control iPSC-NK cells. Overall, our study provided evidence that iPSC derived-NK cells engineered with CD226 represent a promising candidate for off-the-shelf immunotherapy, particularly in AML and other CD226 ligand-expressing malignancies.https://doi.org/10.1186/s40164-025-00686-9Acute myeloid leukemiaiPSC-derived NK cellsCD226Immunotherapy |
| spellingShingle | Runze Cai Binyan Lu Xiangyu Zhao Shixin Zhou Yang Li iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia Experimental Hematology & Oncology Acute myeloid leukemia iPSC-derived NK cells CD226 Immunotherapy |
| title | iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia |
| title_full | iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia |
| title_fullStr | iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia |
| title_full_unstemmed | iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia |
| title_short | iPSC-derived NK cells engineered with CD226 effectively control acute myeloid leukemia |
| title_sort | ipsc derived nk cells engineered with cd226 effectively control acute myeloid leukemia |
| topic | Acute myeloid leukemia iPSC-derived NK cells CD226 Immunotherapy |
| url | https://doi.org/10.1186/s40164-025-00686-9 |
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