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In this study, programmed cell death protein 1 (PD1)\u2010expressing hematopoietic stem cells (HSCs) are genetically engineered for bone\u2010targeted delivery of the transforming growth factor beta (TGF\u2010<jats:italic>\u03b2<\/jats:italic>) small\u2010molecule inhibitor SB\u2010505124 (SB@HSCs\u2010PD\u20101). Intriguingly, compared to anti\u2010PD\u2010L1 monoclonal antibodies, as \u201cliving drugs\u201d, HSCs\u2010PD\u20101 not only show great targeting ability to the bone marrow, but are also able to reduplicate themselves within the bone marrow niche and continuously express PD\u20101 molecules. The SB released from HSCs\u2010PD\u20101 competitively bound to TGF\u2010<jats:italic>\u03b2<\/jats:italic> receptors on CD4<jats:sup>+<\/jats:sup> T cells and facilitate CD4<jats:sup>+<\/jats:sup> T cell differentiation to helper T (T<jats:sub>H<\/jats:sub>)1 and T<jats:sub>H<\/jats:sub>2 cells, thereby reprogramming the local immunosuppressive milieu of the bone marrow. 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In conclusion, in the present study, an alternative cell engineering strategy is delineated for immune checkpoint blockade therapy, to target bone metastasis using HSCs as a platform, which shows great promise in the treatment of bone metastases.<\/jats:p>","DOI":"10.1002\/advs.202201451","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T22:01:30Z","timestamp":1660168890000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Genetically Engineered Hematopoietic Stem Cells Deliver TGF\u2010<i>\u03b2<\/i> Inhibitor to Enhance Bone Metastases Immunotherapy"],"prefix":"10.1002","volume":"9","author":[{"given":"Beilei","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon\u2010Based Functional Materials &amp; Devices Soochow University  199 Ren'ai Road Suzhou Jiangsu 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Soochow University  Suzhou Jiangsu 215004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Soochow University  Suzhou Jiangsu 215004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The Second Affiliated Hospital of Soochow University  Suzhou Jiangsu 215004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; 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