{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:14:44Z","timestamp":1789568084554,"version":"build-2803163510"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Ruichuang Biotechnology Co., Ltd."},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20453, 82270223 and 82170209"],"award-info":[{"award-number":["U23A20453, 82270223 and 82170209"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anhui Provincial Key Research and Development Project","award":["2022e07020015"],"award-info":[{"award-number":["2022e07020015"]}]},{"name":"Anhui Health Research Project","award":["AHWJ2022a011"],"award-info":[{"award-number":["AHWJ2022a011"]}]},{"name":"Anhui Provincial Department of Education Scientific Research Project","award":["2023AH010079, 2022AH030128"],"award-info":[{"award-number":["2023AH010079, 2022AH030128"]}]},{"DOI":"10.13039\/501100003995","name":"Anhui Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["2308085J09"],"award-info":[{"award-number":["2308085J09"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"crossref"}]},{"name":"International Cooperation Projects in Anhui Province","award":["2023h11020005"],"award-info":[{"award-number":["2023h11020005"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Relapse remains a major challenge for high-risk acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). In our first-in-human Phase I trial (ChiCTR-1900022795), we have demonstrated that third-party donor-derived double-negative T cells (DNTs) are safe and effective for treating relapsed AML. This Phase I study aims to further evaluate the safety and efficacy of allo-DNTs in preventing relapse in AML patients post-allo-HSCT. Six high-risk AML patients received three infusions of off-the-shelf allo-DNTs at one-month intervals, administered 60 to 100 days post-allo-HSCT without lymphodepleting chemotherapy. No dose-limiting toxicity, DNT-related graft-versus-host disease (GvHD), or severe cytokine release syndrome (CRS) occurred. With a median follow-up of 20.9 months (range: 11.4\u201324.6), four patients (66.7%) remained in minimal residual disease (MRD)-negative complete remission (CR), with recurrence-free survival exceeding 24 months. Patients in remission showed increased CD8\u207a and CD4\u207a T cells, total DNTs, and higher frequencies of granzyme-secreting T cells, which were absent in relapsed patients. In vitro, co-culturing AML patient CD8\u207a T cells with allo-DNTs upregulated granzyme B and interferon-\u03b3 expression, indicating CD8\u207a T cell activation. These findings suggest that allogeneic DNT immunotherapy is a safe, promising strategy to prevent relapse in high-risk AML patients post-allo-HSCT by combining intrinsic antitumor activity with immune modulation.<\/jats:p>","DOI":"10.1186\/s40164-025-00680-1","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:53:06Z","timestamp":1751464386000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prophylactic infusion of allogeneic double-negative T cells as immune modulators to prevent relapse in high-risk AML patients post-Allo-HSCT: a phase I trial"],"prefix":"10.1186","volume":"14","author":[{"given":"Guangyu","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaidi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haicun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"issue":"11","key":"680_CR1","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1038\/bmt.2016.167","volume":"51","author":"P Tsirigotis","year":"2016","unstructured":"Tsirigotis P, Byrne M, Schmid C, Baron F, Ciceri F, Esteve J, et al. Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transpl. 2016;51(11):1431\u20138.","journal-title":"Bone Marrow Transpl"},{"issue":"3","key":"680_CR2","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.bbmt.2014.11.007","volume":"21","author":"N Bejanyan","year":"2015","unstructured":"Bejanyan N, Weisdorf DJ, Logan BR, Wang HL, Devine SM, de Lima M, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transpl. 2015;21(3):454\u20139.","journal-title":"Biol Blood Marrow Transpl"},{"issue":"1","key":"680_CR3","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13045-019-0751-4","volume":"12","author":"S Piemontese","year":"2019","unstructured":"Piemontese S, Boumendil A, Labopin M, Schmid C, Ciceri F, Arcese W, et al. Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT. J Hematol Oncol. 2019;12(1):68.","journal-title":"J Hematol Oncol"},{"key":"680_CR4","doi-asserted-by":"crossref","unstructured":"Zuanelli Brambilla C, Lobaugh SM, Ruiz JD, Dahi PB, Goldberg AD, Young JW et al. Relapse after Allogeneic Stem Cell Transplantation of Acute Myelogenous Leukemia and Myelodysplastic Syndrome and the Importance of Second Cellular Therapy. Transplant Cell Ther. 2021;27(9):771.e1-.e10.","DOI":"10.1016\/j.jtct.2021.05.011"},{"issue":"4","key":"680_CR5","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/bmt.2014.300","volume":"50","author":"T Sauer","year":"2015","unstructured":"Sauer T, Silling G, Groth C, Rosenow F, Krug U, G\u00f6rlich D, et al. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT. Bone Marrow Transpl. 2015;50(4):485\u201392.","journal-title":"Bone Marrow Transpl"},{"key":"680_CR6","doi-asserted-by":"publisher","first-page":"217264","DOI":"10.1016\/j.canlet.2024.217264","volume":"605","author":"Y Wang","year":"2024","unstructured":"Wang Y, Chang YJ, Chen J, Han M, Hu J, Hu J, et al. Consensus on the monitoring, treatment, and prevention of leukaemia relapse after allogeneic Haematopoietic stem cell transplantation in china: 2024 update. Cancer Lett. 2024;605:217264.","journal-title":"Cancer Lett"},{"issue":"1","key":"680_CR7","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13046-024-03247-w","volume":"44","author":"J Lee","year":"2025","unstructured":"Lee J, Kang H, Chen B, Na Y, Khatri I, Soares F, et al. Allogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD. J Exp Clin Cancer Res. 2025;44(1):28.","journal-title":"J Exp Clin Cancer Res"},{"issue":"7","key":"680_CR8","doi-asserted-by":"publisher","first-page":"E264","DOI":"10.1002\/ajh.26564","volume":"97","author":"B Tang","year":"2022","unstructured":"Tang B, Lee JB, Cheng S, Pan T, Yao W, Wang D, et al. Allogeneic double-negative T cell therapy for relapsed acute myeloid leukemia patients post allogeneic hematopoietic stem cell transplantation: A first-in-human phase I study. Am J Hematol. 2022;97(7):E264\u20137.","journal-title":"Am J Hematol"}],"container-title":["Experimental Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-025-00680-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40164-025-00680-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-025-00680-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:53:07Z","timestamp":1751464387000},"score":1,"resource":{"primary":{"URL":"https:\/\/ehoonline.biomedcentral.com\/articles\/10.1186\/s40164-025-00680-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":8,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["680"],"URL":"https:\/\/doi.org\/10.1186\/s40164-025-00680-1","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,2]]},"assertion":[{"value":"26 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in accordance with the Declaration of Helsinki and was approved by the ethics committee of the First Affiliated Hospital of the University of Science and Technology of China.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors are consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Liming Yang & Haicun Xie are employed by Ruichuang Biotechnology Co., Ltd., Shaoxing, China. Liming Yang is inventor of several DNT technology-related patents and intellectual properties. The remaining authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"90"}}