{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:10:44Z","timestamp":1792239044772,"version":"4.4.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acute myeloid leukaemia (AML) is often aggressive and life-threatening with limited curative options. Immunotherapies including chimeric antigen receptor (CAR) T-cell approaches are under investigation, but high levels of disease heterogeneity remain a major hurdle to achieving durable responses. Targeting of multiple antigens may ensure complete immunological coverage of leukaemic blast populations, but such antigens are often also present on healthy haematopoietic populations. To address likely aplasia, strategies can be designed to bridge CAR T-cell therapies to allogeneic stem-cell transplantation (allo-SCT), as demonstrated in recent anti-CD7 CAR T-cell studies. Here we report that monotherapy using base edited \u201cuniversal\u201d donor CAR T cells against CD33, CLL-1, or CD7 delivered inhibition of AML in immunodeficient mice when antigen expression was homogenous, but combined use of BE-CAR33 and BE-CARCLL-1 T cells was required to address heterogenous CLL-1\n                    <jats:sup>-\/+<\/jats:sup>\n                    CD33\n                    <jats:sup>-\/+<\/jats:sup>\n                    disease. We also demonstrate that removal of shared CD7 antigens enabled compatibility of BE-CAR33 and BE-CARCLL-1 with BE-CAR7 T cells, including in a patient-derived xenograft (PDX) model of AML. Therapeutic strategies envisage \u2018pick and mix\u2019 applications of base edited \u201cuniversal\u201d CAR T cells in combination determined by patient-specific antigen profiles. Such approaches also offer the possibility of deep, cell-based, de-bulking and conditioning ahead of allo-SCT and subsequent donor-derived reconstitution.\n                  <\/jats:p>","DOI":"10.1038\/s41375-025-02720-5","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T07:44:07Z","timestamp":1759304647000},"page":"2978-2987","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Base edited \u201cuniversal\u201d donor CAR T-cell strategies for acute myeloid leukaemia"],"prefix":"10.1038","volume":"39","author":[{"given":"Renuka","family":"Kadirkamanathan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-8396","authenticated-orcid":false,"given":"Christos","family":"Georgiadis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Kloos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Etuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Preece","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4737-1023","authenticated-orcid":false,"given":"Oliver","family":"Gough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2743-0070","authenticated-orcid":false,"given":"Axel","family":"Schambach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2151-8342","authenticated-orcid":false,"given":"Martin","family":"Sauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-9044","authenticated-orcid":false,"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8353-4494","authenticated-orcid":false,"given":"Waseem","family":"Qasim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"2720_CR1","first-page":"2813","volume":"141","author":"F El Chaer","year":"2023","unstructured":"El Chaer F, Hourigan CS, Zeidan AM. How I treat AML incorporating the updated classifications and guidelines. Blood. 2023;141:2813\u201323.","journal-title":"Blood"},{"key":"2720_CR2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1182\/blood-2015-07-604546","volume":"127","author":"JJ Cornelissen","year":"2016","unstructured":"Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood. 2016;127:62\u201370.","journal-title":"Blood"},{"key":"2720_CR3","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1182\/blood.2020006921","volume":"137","author":"S Willier","year":"2021","unstructured":"Willier S, Roth\u00e4mel P, Hastreiter M, Wilhelm J, Stenger D, Blaeschke F, et al. CLEC12A and CD33 coexpression as a preferential target for pediatric AML combinatorial immunotherapy. Blood. 2021;137:1037\u201349.","journal-title":"Blood"},{"key":"2720_CR4","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41375-018-0180-3","volume":"33","author":"S Haubner","year":"2019","unstructured":"Haubner S, Perna F, K\u00f6hnke T, Schmidt C, Berman S, Augsberger C, et al. Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML. Leukemia. 2019;33:64\u201374.","journal-title":"Leukemia"},{"key":"2720_CR5","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1002\/eji.200535628","volume":"36","author":"ASJ Marshall","year":"2006","unstructured":"Marshall ASJ, Willment JA, Pyz E, Dennehy KM, Reid DM, Dri P, et al. Human MICL (CLEC12A) is differentially glycosylated and is down-regulated following cellular activation. Eur J Immunol. 2006;36:2159\u201369.","journal-title":"Eur J Immunol"},{"key":"2720_CR6","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1182\/blood.V81.9.2399.2399","volume":"81","author":"K Kita","year":"1993","unstructured":"Kita K, Miwa H, Nakase K, Kawakami K, Kobayashi T, Shirakawa S, et al. Clinical importance of CD7 expression in acute myelocytic leukemia. Blood. 1993;81:2399\u2013405.","journal-title":"Blood"},{"key":"2720_CR7","first-page":"1261","volume":"86","author":"L Mu\u00f1oz","year":"2001","unstructured":"Mu\u00f1oz L, Nomded\u00e9u JF, L\u00f3pez O, Carnicer MJ, Bellido M, Avent\u00edn A, et al. Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Haematologica. 2001;86:1261\u20139.","journal-title":"Haematologica"},{"key":"2720_CR8","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1182\/blood.V82.3.752.752","volume":"82","author":"N Sato","year":"1993","unstructured":"Sato N, Caux C, Kitamura T, Watanabe Y, Arai K, Banchereau J, et al. Expression and factor-dependent modulation of the interleukin-3 receptor subunits on human hematopoietic cells. Blood. 1993;82:752\u201361.","journal-title":"Blood"},{"key":"2720_CR9","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1182\/blood.V86.1.176.bloodjournal861176","volume":"86","author":"EI Korpelainen","year":"1995","unstructured":"Korpelainen EI, Gamble JR, Smith WB, Dottore M, Vadas MA, Lopez AF. Interferon-\u03b3 upregulates interleukin-3 (IL-3) receptor expression in human endothelial cells and synergizes with IL-3 in stimulating major histocompatibility complex class II expression and cytokine production. Blood. 1995;86:176\u201382.","journal-title":"Blood"},{"key":"2720_CR10","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.4049\/jimmunol.170.5.2349","volume":"170","author":"EM Aandahl","year":"2003","unstructured":"Aandahl EM, Sandberg JK, Beckerman KP, Task\u00e9n K, Moretto WJ, Nixon DF. CD7 Is a Differentiation Marker That Identifies Multiple CD8 T Cell Effector Subsets. J Immunol. 2003;170:2349\u201355.","journal-title":"J Immunol"},{"key":"2720_CR11","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1046\/j.1365-2141.2003.04500.x","volume":"122","author":"PD Kottaridis","year":"2003","unstructured":"Kottaridis PD, Gale RE, Linch DC. FLT3 mutations and leukaemia. Br J Haematol. 2003;122:523\u201338.","journal-title":"Br J Haematol"},{"key":"2720_CR12","doi-asserted-by":"crossref","first-page":"7358","DOI":"10.4049\/jimmunol.180.11.7358","volume":"180","author":"Y Kikushige","year":"2008","unstructured":"Kikushige Y, Yoshimoto G, Miyamoto T, Iino T, Mori Y, Iwasaki H, et al. Human Flt3 Is Expressed at the Hematopoietic Stem Cell and the Granulocyte\/Macrophage Progenitor Stages to Maintain Cell Survival. J Immunol. 2008;180:7358\u201367.","journal-title":"J Immunol"},{"key":"2720_CR13","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1038\/s41375-021-01282-6","volume":"35","author":"C Georgiadis","year":"2021","unstructured":"Georgiadis C, Rasaiyaah J, Gkazi SA, Preece R, Etuk A, Christi A, et al. Base-edited CAR T cells for combinational therapy against T cell malignancies. Leukemia. 2021;35:3466\u201381.","journal-title":"Leukemia"},{"key":"2720_CR14","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1056\/NEJMoa2313812","volume":"390","author":"Y Hu","year":"2024","unstructured":"Hu Y, Zhang M, Yang T, Mo Z, Wei G, Jing R, et al. Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis. N Engl J Med. 2024;390:1467\u201380.","journal-title":"N Engl J Med"},{"key":"2720_CR15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ccr.2014.01.031","volume":"25","author":"JM Klco","year":"2014","unstructured":"Klco JM, Spencer DH, Miller CA, Griffith M, Lamprecht TL, O\u2019Laughlin M, et al. Functional heterogeneity of genetically defined subclones in acute myeloid leukemia. Cancer Cell. 2014;25:379\u201392.","journal-title":"Cancer Cell"},{"key":"2720_CR16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymthe.2024.11.028","volume":"33","author":"M Bachiller","year":"2025","unstructured":"Bachiller M, Barcel\u00f3-genestar N, Rodriguez-garcia A, Alserawan L, Doba\u00f1o-l\u00f3pez C, Gim\u00e9nez-alejandre M, et al. Co-transduced CD19 \/ BCMA dual-targeting CAR-T cells for the treatment of non-Hodgkin lymphoma. Mol Ther. 2025;33:1\u201319.","journal-title":"Mol Ther"},{"key":"2720_CR17","doi-asserted-by":"crossref","unstructured":"Shi M, Wang J, Huang H, Liu D, Cheng H, Wang X, et al. Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed\/refractory multiple myeloma: a phase I\/II trial. Nat Commun. 2024;15:3371.","DOI":"10.1038\/s41467-024-47801-8"},{"key":"2720_CR18","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.ymthe.2018.02.025","volume":"26","author":"C Georgiadis","year":"2018","unstructured":"Georgiadis C, Preece R, Nickolay L, Etuk A, Petrova A, Ladon D, et al. Long Terminal Repeat CRISPR-CAR-Coupled \u201cUniversal\u201d T Cells Mediate Potent Anti-leukemic Effects. Mol Ther. 2018;26:1215\u201327.","journal-title":"Mol Ther"},{"key":"2720_CR19","unstructured":"Ottaviano G, Georgiadis C, Gkazi SA, Syed F, Zhan H, Etuk A, et al. Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia. Sci Transl Med. 2022;14:eabq3010."},{"key":"2720_CR20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-022-29668-9","volume":"13","author":"M Sugita","year":"2022","unstructured":"Sugita M, Galetto R, Zong H, Ewing-Crystal N, Trujillo-Alonso V, Mencia-Trinchant N, et al. Allogeneic TCR\u03b1\u03b2 deficient CAR T-cells targeting CD123 in acute myeloid leukemia. Nat Commun. 2022;13:1\u201311.","journal-title":"Nat Commun"},{"key":"2720_CR21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-07584-1","volume":"9","author":"S Chaudhury","year":"2018","unstructured":"Chaudhury S, O\u2019Connor C, Ca\u00f1ete A, Bittencourt-Silvestre J, Sarrou E, Prendergast \u00c1, et al. Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias. Nat Commun. 2018;9:1\u201314.","journal-title":"Nat Commun"},{"key":"2720_CR22","first-page":"1","volume":"12","author":"L Davis","year":"2020","unstructured":"Davis L, Mills KI, Orchard KH, Guinn BA. Identification of genes whose expression overlaps age boundaries and correlates with risk groups in paediatric and adult acute myeloid leukaemia. Cancers. 2020;12:1\u201322.","journal-title":"Cancers"},{"key":"2720_CR23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/pbc.28099","volume":"67","author":"K Klein","year":"2020","unstructured":"Klein K, van Litsenburg RRL, de Haas V, Dors N, van den Heuvel-Eibrink MM, Knops RRG, et al. Causes of early death and treatment-related death in newly diagnosed pediatric acute myeloid leukemia: Recent experiences of the Dutch Childhood Oncology Group. Pediatr Blood Cancer. 2020;67:1\u201310.","journal-title":"Pediatr Blood Cancer"},{"key":"2720_CR24","doi-asserted-by":"crossref","unstructured":"Wasylyshyn AI, Linder KA, Kauffman CA, Richards BJ, Maurer SM, Sheffield VM, et al. Invasive fungal disease in patients with newly diagnosed acute myeloid leukemia. J Fungi. 2021;7:761.","DOI":"10.3390\/jof7090761"},{"key":"2720_CR25","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/cncr.26190","volume":"118","author":"TM Cooper","year":"2012","unstructured":"Cooper TM, Franklin J, Gerbing RB, Alonzo TA, Hurwitz C, Raimondi SC, et al. AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: A report from the Children\u2019s Oncology Group. Cancer. 2012;118:761\u20139.","journal-title":"Cancer"},{"key":"2720_CR26","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S1470-2045(14)70281-5","volume":"15","author":"RK Hills","year":"2014","unstructured":"Hills RK, Castaigne S, Appelbaum FR, Delaunay J, Petersdorf S, Othus M, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: A meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol. 2014;15:986\u201396.","journal-title":"Lancet Oncol"},{"key":"2720_CR27","first-page":"5908s","volume":"55","author":"JG Jurcic","year":"1995","unstructured":"Jurcic JG, Caron PC, Nikula TK, Papadopoulos EB, Finn RD, Gansow OA, et al. Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias. Cancer Res. 1995;55:5908s\u20135910s.","journal-title":"Cancer Res"},{"key":"2720_CR28","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1038\/leu.2015.52","volume":"29","author":"SS Kenderian","year":"2015","unstructured":"Kenderian SS, Ruella M, Shestova O, Klichinsky M, Aikawa V, Morrissette JJD, et al. CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia. 2015;29:1637\u201347.","journal-title":"Leukemia"},{"key":"2720_CR29","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1182\/blood-2017-06-789800","volume":"131","author":"EM Stein","year":"2018","unstructured":"Stein EM, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, et al. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood. 2018;131:387\u201396.","journal-title":"Blood"},{"key":"2720_CR30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cts.13742","volume":"17","author":"R Narayan","year":"2024","unstructured":"Narayan R, Pi\u00e9rola AA, Donnellan WB, Yordi AM, Abdul-Hay M, Platzbecker U, et al. First-in-human study of JNJ-67571244, a CD33 \u00d7 CD3 bispecific antibody, in relapsed\/refractory acute myeloid leukemia and myelodysplastic syndrome. Clin Transl Sci. 2024;17:1\u201318.","journal-title":"Clin Transl Sci"},{"key":"2720_CR31","doi-asserted-by":"crossref","unstructured":"Qin H, Yang L, Chukinas JA, Shah N, Tarun S, Pouzolles M, et al. Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design. J Immunother Cancer 2021;9:e003149.","DOI":"10.1136\/jitc-2021-003149"},{"key":"2720_CR32","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1182\/blood-2023-179667","volume":"142","author":"NN Shah","year":"2023","unstructured":"Shah NN, Tasian SK, Kohler ME, Hsieh EM, Baumeister SHC, Summers C, et al. CD33 CAR T-Cells (CD33CART) for Children and Young Adults with Relapsed\/Refractory AML: Dose-Escalation Results from a Phase I\/II Multicenter Trial. Blood. 2023;142:771\u2013771.","journal-title":"Blood"},{"key":"2720_CR33","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.1038\/s41375-021-01232-2","volume":"35","author":"FP Tambaro","year":"2021","unstructured":"Tambaro FP, Singh H, Jones E, Rytting M, Mahadeo KM, Thompson P, et al. Autologous CD33-CAR-T cells for treatment of relapsed\/refractory acute myelogenous leukemia. Leukemia. 2021;35:3282\u20136.","journal-title":"Leukemia"},{"key":"2720_CR34","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/mt.2014.164","volume":"23","author":"QS Wang","year":"2015","unstructured":"Wang QS, Wang Y, Lv HY, Han QW, Fan H, Guo B, et al. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther. 2015;23:184\u201391.","journal-title":"Mol Ther"},{"key":"2720_CR35","doi-asserted-by":"crossref","first-page":"10313","DOI":"10.1182\/blood-2022-169142","volume":"140","author":"DA Sallman","year":"2022","unstructured":"Sallman DA, Elmariah H, Sweet K, Mishra A, Cox CA, Chakaith M, et al. Phase 1\/1b Safety Study of Prgn-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-positive acute myeloid leukemia and higher risk myelodysplastic syndromes. Blood. 2022;140:10313\u20135.","journal-title":"Blood"},{"key":"2720_CR36","doi-asserted-by":"crossref","unstructured":"Appelbaum J, Price AE, Oda K, Zhang J, Leung WH, Tampella G, et al. Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing. J Clin Invest. 2024;134:e162593.","DOI":"10.1172\/JCI162593"},{"key":"2720_CR37","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1182\/blood-2007-03-083048","volume":"110","author":"A Van Rhenen","year":"2007","unstructured":"Van Rhenen A, Van Dongen GAMS, Kelder A, Le, Rombouts EJ, Feller N, et al. The novel AML stem cell-associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood. 2007;110:2659\u201366.","journal-title":"Blood"},{"key":"2720_CR38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fonc.2020.00001","volume":"10","author":"H Zhang","year":"2020","unstructured":"Zhang H, Gan WT, Hao WG, Wang PF, Li ZY, Chang LJ. Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia. Front Oncol. 2020;10:1\u20136.","journal-title":"Front Oncol"},{"key":"2720_CR39","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1158\/1078-0432.CCR-20-4543","volume":"27","author":"H Zhang","year":"2021","unstructured":"Zhang H, Wang P, Li Z, He Y, Gan W, Jiang H. Anti-CLL1 chimeric antigen receptor T-cell therapy in children with relapsed\/refractory acute myeloid leukemia. Clin Cancer Res. 2021;27:3549\u201355.","journal-title":"Clin Cancer Res"},{"key":"2720_CR40","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1038\/s41375-022-01703-0","volume":"36","author":"H Zhang","year":"2022","unstructured":"Zhang H, Bu C, Peng Z, Li G, Zhou Z, Ding W, et al. Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis. Leukemia. 2022;36:2596\u2013604.","journal-title":"Leukemia"},{"key":"2720_CR41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13045-022-01308-1","volume":"15","author":"X Jin","year":"2022","unstructured":"Jin X, Zhang M, Sun R, Lyu H, Xiao X, Zhang X, et al. First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed\/refractory acute myeloid leukemia. J Hematol Oncol. 2022;15:88.","journal-title":"J Hematol Oncol"},{"key":"2720_CR42","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jcyt.2021.10.007","volume":"24","author":"PA Atilla","year":"2022","unstructured":"Atilla PA, McKenna MK, Watanabe N, Mamonkin M, Brenner MK, Atilla E. Combinatorial antigen targeting strategies for acute leukemia: application in myeloid malignancy. Cytotherapy. 2022;24:282\u201390.","journal-title":"Cytotherapy"},{"key":"2720_CR43","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1182\/blood-2018-99-110579","volume":"132","author":"F Liu","year":"2018","unstructured":"Liu F, Cao Y, Pinz K, Ma Y, Wada M, Chen K, et al. First-in-Human CLL1-CD33 Compound CAR T Cell Therapy Induces Complete Remission in Patients with Refractory Acute Myeloid Leukemia: Update on Phase 1 Clinical Trial. Blood. 2018;132:901\u2013901.","journal-title":"Blood"},{"key":"2720_CR44","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1046\/j.1365-2141.2001.03139.x","volume":"115","author":"K Ogata","year":"2001","unstructured":"Ogata K, Yokose N, Shioi Y, Ishida Y, Tomiyama J, Hamaguchi H, et al. Reappraisal of the clinical significance of CD7 expression in association with cytogenetics in de novo acute myeloid leukaemia. Br J Haematol. 2001;115:612\u20135.","journal-title":"Br J Haematol"},{"key":"2720_CR45","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1056\/NEJMoa2300709","volume":"389","author":"R Chiesa","year":"2023","unstructured":"Chiesa R, Georgiadis C, Syed F, Zhan H, Etuk A, Gkazi SA, et al. Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia. N Engl J Med. 2023;389:899\u2013910.","journal-title":"N Engl J Med"},{"key":"2720_CR46","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1182\/blood-2023-190037","volume":"142","author":"J DiPersio","year":"2023","unstructured":"DiPersio J, Cooper BW, Suh HC, Koura D, Bernard L, Shah NN, et al. Trem-Cel, a CRISPR\/Cas9 Gene-Edited Allograft Lacking CD33, Shows Rapid Primary Engraftment with CD33-Negative Hematopoiesis in Patients with High-Risk Acute Myeloid Leukemia (AML) and Avoids Hematopoietic Toxicity during Gemtuzumab Ozogamicin (GO) Maintenance Post-Hematopoietic Cell Transplant (HCT). Blood. 2023;142:483\u2013483.","journal-title":"Blood"},{"key":"2720_CR47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.adi1145","volume":"15","author":"N Wellhausen","year":"2023","unstructured":"Wellhausen N, O\u2019Connell RP, Lesch S, Engel NW, Rennels AK, Gonzales D, et al. Epitope base editing CD45 in hematopoietic cells enables universal blood cancer immune therapy. Sci Transl Med. 2023;15:1\u201315.","journal-title":"Sci Transl Med"},{"key":"2720_CR48","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/s41586-024-07456-3","volume":"630","author":"S Garaud\u00e9","year":"2024","unstructured":"Garaud\u00e9 S, Marone R, Lepore R, Devaux A, Beerlage A, Seyres D, et al. Selective haematological cancer eradication with preserved haematopoiesis. Nature. 2024;630:728\u201335.","journal-title":"Nature"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-025-02720-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-025-02720-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-025-02720-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T09:10:23Z","timestamp":1763629823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-025-02720-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["2720"],"URL":"https:\/\/doi.org\/10.1038\/s41375-025-02720-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.28.630573","asserted-by":"object"}]},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"assertion":[{"value":"11 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"W.Q has advised Virocell, Wugen & Galapagos. MH declares honoraria from Abbvie, Bristol Myers Squibb, Janssen, Jazz Pharmaceuticals, Pfizer, Qiagen, Servier, Sobi, paid consultancy for AvenCell, Abbvie, Astellas, Glycostem, Janssen, LabDelbert, Miltenyi, Novartis, Pfizer, PinotBio, Servier, and research funding to his institution from Abbvie, Servier, Astellas, BergenBio, Glycostem, Jazz Pharmaceuticals, Karyopharm, Loxo Oncology, Novartis, PinotBio.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All methods were performed in accordance with approved guidelines from the University College London Research Ethics Committee (REC Reference: 25257.001) and Nolan Registry (REC Reference No.: 19\/LO\/0447). Informed consent was obtained from all healthy volunteer donors. Animal studies were approved by the UCL Biological Services Ethical Review Committee (Reference No.: PP5675666) and licensed under the Animals (Scientific Procedures) Act 1986 (Home Office, London, United Kingdom). The PDX mouse model, established at Hannover Medical School, was conducted with approval from the Lower Saxony state office for consumer protection, Oldenburg, Germany (Reference No.: 22-00042).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}