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This highlights the urgent need for novel therapies aimed at eliminating these CML-LSCs. Chimeric antigen receptor macrophages (CAR-M) not only perform phagocytosis on target cells but also function as antigen-presenting cells, thereby activating the anti-tumor immune response.CD26 (dipeptidyl peptidase 4, DPP IV) is abundantly expressed in CML-LSCs and functions as a tumor-specific antigen (TSA) in CAR-M treatment. The purpose of this study is to evaluate CAR-M\u2019s efficacy in targeting CD26-positive CML cells and to develop a novel strategy for CML treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CD26 CAR-M was constructed using mouse-derived macrophage Raw264.7 cells. CD26 was overexpressed in CML cell lines BP210 and BP210-T315I. The targeting phagocytosis of CAR-M was verified using confocal microscopy and flow cytometry. X-ray was used to eliminate the tumorigenicity of CAR-M, and the safety of CAR-M was verified through CCK-8, clone formation assays, and animal experiments. To assess the anti-leukemia ability of CAR-M in the CML mouse model, the survival, peripheral blood white blood cell counts, and CML cell infiltration in the liver, spleen, and bone marrow (BM) were measured. Additionally, CD26 CAR-THP1 was constructed, and its phagocytic ability against CD26-positive cells NCI-H2452 was confirmed by confocal microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We successfully constructed CD26 CAR-M and validated its targeted phagocytosis of CD26-positive CML cells both in vitro and in vivo. The data indicate that CAR-M has higher phagocytic efficiency in CD26-positive CML cells than in CD26-negative cells. CAR-M-treated CML mice demonstrated extended survival and reduced CML invasion. In addition, CAR-THP1 demonstrated targeted phagocytosis of NCI-H2452 cells that normally express CD26.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that CD26 CAR-M effectively targets and phagocytizes CD26-positive CML cells, implying that targeting CD26 with CAR-M could be a viable method for eradicating CML-LSCs. Furthermore, our discoveries illuminate the potential application of CAR-M in treating hematological malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40164-025-00608-9","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T03:35:07Z","timestamp":1739417707000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["CAR-macrophages targets CD26 to eliminate chronic myeloid leukemia stem cells"],"prefix":"10.1186","volume":"14","author":[{"given":"Jiang","family":"Guoyun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yuefeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Zhenglan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zuowei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Hongyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wenli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"issue":"1","key":"608_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.6004\/jnccn.2024.0007","volume":"22","author":"NP Shah","year":"2024","unstructured":"Shah NP, Bhatia R, Altman JK, Amaya M, Begna KH, Berman E, Chan O, Clements J, Collins RH, Curtin PT, et al. 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