{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:29Z","timestamp":1787027789163,"version":"build-2736575974"},"reference-count":125,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chimeric antigen receptors (CAR)-T-cell therapy represents the most important innovation in onco-hematology in recent years. The progress achieved in the management of complications and the latest generations of CAR-T-cells have made it possible to anticipate in second-line the indication of this type of treatment in large B-cell lymphoma. While some types of B-cell lymphomas and B-cell acute lymphoid leukemia have shown extremely promising results, the same cannot be said for myeloid leukemias\u2014in particular, acute myeloid leukemia (AML), which would require innovative therapies more than any other blood disease. The heterogeneities of AML cells and the immunological complexity of the interactions between the bone marrow microenvironment and leukemia cells have been found to be major obstacles to the clinical development of CAR-T in AML. In this review, we report on the main results obtained in AML clinical trials, the preclinical studies testing potential CAR-T constructs, and future perspectives.<\/jats:p>","DOI":"10.3390\/cancers16010042","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T11:24:33Z","timestamp":1703071473000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Chimeric Antigen Receptor T-Cell Therapy in Acute Myeloid Leukemia: State of the Art and Recent Advances"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4703-6280","authenticated-orcid":false,"given":"Martina","family":"Canichella","sequence":"first","affiliation":[{"name":"Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-4406","authenticated-orcid":false,"given":"Matteo","family":"Molica","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Mazzone","sequence":"additional","affiliation":[{"name":"Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"de Fabritiis","sequence":"additional","affiliation":[{"name":"Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy"},{"name":"Department of Biomedicina e Prevenzione, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"ref_1","first-page":"e441","article-title":"Acute myeloid leukemia: A comprehensive review and 2016 update","volume":"7","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_2","first-page":"62","article-title":"Hematopoietic stem cell transplantation for patients with AML in first complete remission","volume":"127","author":"Cornelissen","year":"2016","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1056\/NEJMoa2116133","article-title":"All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma","volume":"7","author":"Locke","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"26","author":"Neelapu","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia","volume":"5","author":"Maude","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1470-2045(21)00591-X","article-title":"Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): A single-arm, multicentre, phase 2 trial","volume":"1","author":"Jacobson","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/s41591-022-01731-4","article-title":"Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: The phase 2 ZUMA-12 trial","volume":"28","author":"Neelapu","year":"2022","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0140-6736(21)01222-8","article-title":"KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: Phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study","volume":"398","author":"Shah","year":"2021","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma","volume":"1","author":"Schuster","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","article-title":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study","volume":"396","author":"Abramson","year":"2020","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1056\/NEJMoa1914347","article-title":"KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma","volume":"14","author":"Wang","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41591-021-01622-0","article-title":"Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: The phase 2 ELARA trial","volume":"2","author":"Fowler","year":"2022","journal-title":"Nat Med."},{"key":"ref_13","first-page":"335","article-title":"Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma","volume":"4","author":"Dhakal","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/imr.12126","article-title":"CAR T cells: Driving the road from the laboratory to the clinic","volume":"257","author":"Cheadle","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2217\/imt-2016-0103","article-title":"Tumor-targeting domains for chimeric antigen receptor T cells","volume":"1","author":"Bezverbnaya","year":"2017","journal-title":"Immunotherapy"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Safarzadeh Kozani, P., Naseri, A., Mirarefin, S.M.J., Salem, F., Nikbakht, M., Evazi Bakhshi, S., and Safarzadeh Kozani, P. (2022). Nanobody-based CAR-T cells for cancer immunotherapy. Biomark. Res., 1.","DOI":"10.1186\/s40364-022-00371-7"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6938","DOI":"10.4049\/jimmunol.0901766","article-title":"The optimal antigen response of chimeric antigen receptors harboring the CD3zeta transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR\/CD3 complex","volume":"12","author":"Bridgeman","year":"2010","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/imr.12131","article-title":"Design and development of therapies using chimeric antigen receptor-expressing T cells","volume":"1","author":"Dotti","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/j.ymthe.2017.07.013","article-title":"Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions is Affected by Hinge and Transmembrane Domains","volume":"11","author":"Alabanza","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1084\/jem.181.5.1653","article-title":"Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes","volume":"181","author":"Brocker","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nm827","article-title":"Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15","volume":"9","author":"Brentjens","year":"2003","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1158\/2159-8290.CD-17-0263","article-title":"Inducible Activation of MyD88 and CD40 in CAR T Cells Results in Controllable and Potent Antitumor Activity in Preclinical Solid Tumor Models","volume":"11","author":"Mata","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"458","DOI":"10.4161\/onci.19855","article-title":"OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4(+) T cells","volume":"4","author":"Hombach","year":"2012","journal-title":"Oncoimmunology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, C., Liu, J., Zhong, J.F., and Zhang, X. (2017). Engineering CAR-T cells. Biomark. Res., 24.","DOI":"10.1186\/s40364-017-0102-y"},{"key":"ref_25","first-page":"499","article-title":"The pharmacology of second generation chimeric antigen receptors","volume":"7","author":"Hamieh","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nri1248","article-title":"CD28-mediated co-stimulation: A quantitative support for TCR signalling","volume":"12","author":"Acuto","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jocit.2016.08.001","article-title":"Chimeric antigen receptor (Car) T cell therapy for malignant cancers: Summary and perspective","volume":"2","author":"Smith","year":"2016","journal-title":"J. Cell. Immunother."},{"key":"ref_28","first-page":"5047","article-title":"How Do Cytotoxic Lymphocytes Kill Cancer Cells?","volume":"22","author":"Anel","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1089\/hum.2015.054","article-title":"CAR T-Cell Therapy: The Role of Physical Barriers and Immunosuppression in Lymphoma","volume":"8","author":"Enblad","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nm.4478","article-title":"A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects","volume":"3","author":"Kagoya","year":"2018","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4086","DOI":"10.1182\/blood-2005-03-1072","article-title":"Hematopoietic stem cells express multiple myeloid markers: Implications for the origin and targeted therapy of acute myeloid leukemia","volume":"13","author":"Taussig","year":"2005","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s40259-021-00477-8","article-title":"CAR-T Cell Therapy for Acute Myeloid Leukemia: Preclinical Rationale, Current Clinical Progress, and Barriers to Success","volume":"35","author":"Fiorenza","year":"2021","journal-title":"BioDrugs"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/mt.2014.164","article-title":"Treatment of Cd33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia","volume":"23","author":"Wang","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_34","first-page":"1083","article-title":"First-in man clinical trial of CAR NK-92 cells: Safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia","volume":"8","author":"Tang","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_35","unstructured":"Budde, L.E. (2019). 1st European CAR T Cell Meeting Report, European Haematology Association."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bu, C., Peng, Z., Luo, M., Guangchao, L., and Chunfu, L. (2020, January 5\u20138). Phase I clinical trial of autologous CLL1 CAR-T therapy for pediatric patients with relapsed and refractory acute myeloid leukemia. Proceedings of the 62nd Annual ASH Meeting, Virtual.","DOI":"10.1182\/blood-2020-140648"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/gt.2010.174","article-title":"Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor-expressing T cells","volume":"18","author":"Barber","year":"2011","journal-title":"Gene Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1158\/2326-6066.CIR-18-0307","article-title":"Phase I trial of autologous CAR T cells targeting NKG2D ligands in patients with AML\/MDS and multiple myeloma","volume":"7","author":"Baumeister","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/jjco\/hyp194","article-title":"WT1 (Wilms\u2019 Tumor Gene 1): Biology and Cancer Immunotherapy","volume":"5","author":"Sugiyama","year":"2010","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Minagawa, K., Jamil, M.O., Al-Obaidi, M., Pereboeva, L., Salzman, D., Erba, H.P., Lamb, L.S., Bhatia, R., Mineishi, S., and Di Stasi, A. (2016). In vitro pre-clinical validation of suicide gene modified anti-Cd33 redirected chimeric antigen receptor T-cells for acute myeloid leukemia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166891"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1084\/jem.20152008","article-title":"CD70\/CD27 signaling promotes blast stemness and is a viable therapeutic target in acute myeloid leukemia","volume":"2","author":"Riether","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000077554","article-title":"Minimal Residual Disease Studies by Flow Cytometry in Acute Leukemia","volume":"112","author":"Campana","year":"2004","journal-title":"Acta Haematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1182\/blood-2017-07-793760","article-title":"Infectious complications of CD19-targeted chimeric antigen receptor\u2013modified T-cell immunotherapy","volume":"131","author":"Hill","year":"2018","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"El Achi, H., Dupont, E., Paul, S., and Khoury, J.D. (2020). CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies. Cancers, 11.","DOI":"10.3390\/cancers12113087"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.ymthe.2019.04.010","article-title":"Chimeric Antigen Receptors Incorporating D Domains Targeting CD123 Direct Potent Mono- and Bi-specific Antitumor Activity of T Cells","volume":"7","author":"Qin","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1182\/blood-2018-99-110579","article-title":"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","volume":"132","author":"Liu","year":"2018","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1182\/blood-2014-11-612721","article-title":"Targeting of folate receptor \u03b2 on acute myeloid leukemia blasts with chimeric antigen receptor\u2013expressing T cells","volume":"22","author":"Lynn","year":"2015","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/leu.2016.373","article-title":"Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen","volume":"8","author":"Rafiq","year":"2017","journal-title":"Leukemia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22729","DOI":"10.1074\/jbc.274.32.22729","article-title":"OB-BP1\/Siglec-6. a leptin- and sialic acid-binding protein of the immunoglobulin super-family","volume":"32","author":"Patel","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_50","first-page":"98561","article-title":"Universal monitoring of minimal residual disease in acute myeloid leukemia","volume":"3","author":"Song","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13045-017-0553-5","article-title":"Car-T cells targeting cll-1 as an approach to treat acute myeloid leukemia","volume":"11","author":"Wang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.ccell.2022.04.001","article-title":"Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia","volume":"5","author":"Leick","year":"2022","journal-title":"Cancer Cell."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1158\/2159-8290.CD-17-1319","article-title":"Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia","volume":"8","author":"Santomasso","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s41419-018-0918-x","article-title":"The biological basis and clinical symptoms of CAR-T therapy-associated toxicites","volume":"9","author":"Titov","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.exphem.2006.03.003","article-title":"Myeloid precursors and acute myeloid leukemia cells express multiple CD33-related Siglecs","volume":"34","author":"Nguyen","year":"2006","journal-title":"Exp. Hematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1038\/leu.2015.52","article-title":"Cd33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia","volume":"29","author":"Kenderian","year":"2015","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1089\/hum.2017.241","article-title":"Cd33-specific chimeric antigen receptor T cells with different Co-stimulators showed potent anti-leukemia efficacy and different phenotype","volume":"29","author":"Li","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/s41375-017-0008-6","article-title":"Pi3k orchestration of the in vivo persistence of chimeric antigen receptor modified T cells","volume":"32","author":"Zheng","year":"2018","journal-title":"Leukemia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.1038\/s41375-021-01232-2","article-title":"Autologous CD33-CAR-T cells for treatment of relapsed\/refractory acute myelogenous leukemia","volume":"11","author":"Tambaro","year":"2021","journal-title":"Leukemia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1002\/ijc.33865","article-title":"Cd33-directed immunotherapy with third-generation chimeric antigen receptor T cells and gemtuzumab ozogamicin in intact and Cd33-edited acute myeloid leukemia and hematopoietic stem and progenitor cells","volume":"150","author":"Liu","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.3389\/fonc.2019.01358","article-title":"Donor-Derived CD123-Targeted CAR T Cell Serves as a RIC Regimen for Haploidentical Transplantation in a Patient with FUS-ERG+ AML","volume":"3","author":"Yao","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.3389\/fimmu.2020.01787","article-title":"Decitabine-Mediated Epigenetic Reprograming Enhances Anti-leukemia Efficacy of CD123-Targeted Chimeric Antigen Receptor T-Cells","volume":"18","author":"You","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Testa, U., Pelosi, E., and Frankel, A. (2014). Cd 123 is a membrane biomarker and a therapeutic target in hematologic malignancies. Biomark. Res., 2.","DOI":"10.1186\/2050-7771-2-4"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1182\/blood-2002-03-0852","article-title":"Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis","volume":"8","author":"Testa","year":"2002","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1182\/blood-2013-09-529537","article-title":"Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells","volume":"15","author":"Gill","year":"2014","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/bjh.16307","article-title":"Prognostic relevance of CD123 expression in adult AML with normal karyotype","volume":"1","author":"Jiang","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1182\/blood.V126.23.3778.3778","article-title":"First-in-Man Cd123-specific chimeric antigen receptor-modified T cells for the treatment of refractory acute myeloid leukemia","volume":"126","author":"Luo","year":"2015","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1182\/blood-2016-08-736041","article-title":"Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia","volume":"17","author":"Tasian","year":"2017","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.ymthe.2017.04.017","article-title":"Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia","volume":"8","author":"Arcangeli","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_70","first-page":"2659","article-title":"The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells","volume":"7","author":"Kelder","year":"2007","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3324\/haematol.2009.009811","article-title":"Targeting C-type lectin-like molecule-1 for antibody-mediated immunotherapy in acute myeloid leukemia","volume":"1","author":"Zhao","year":"2010","journal-title":"Haematologica"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1016\/j.ymthe.2017.05.024","article-title":"Treatment of Acute Myeloid Leukemia with T Cells Expressing Chimeric Antigen Receptors Directed to C-type Lectin-like Molecule 1","volume":"9","author":"Tashiro","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S167","DOI":"10.1016\/j.bbmt.2018.12.470","article-title":"Optimizing c-type lectin-like molecule 1 (Cll-1) directed car T cell therapy of acute myeloid leukemia","volume":"25","author":"Atilla","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3892\/mmr.2021.11847","article-title":"Cytotoxic effect of CLL-1 CAR-T cell immunotherapy with PD-1 silencing on relapsed\/refractory acute myeloid leukemia","volume":"3","author":"Lin","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13045-022-01308-1","article-title":"First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed\/refractory acute myeloid leukemia","volume":"1","author":"Jin","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1182\/blood-2010-04-278218","article-title":"T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies","volume":"117","author":"Shaffer","year":"2011","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1600-065X.2009.00774.x","article-title":"Timing and tuning of CD27-CD70 interactions: The impact of signal strength in setting the balance between adaptive responses and immunopathology","volume":"1","author":"Nolte","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/s41591-020-0910-8","article-title":"Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents","volume":"26","author":"Riether","year":"2020","journal-title":"Nat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1182\/blood.2020008221","article-title":"CD70-specific CAR T cells have potent activity against acute myeloid leukemia without HSC toxicity","volume":"4","author":"Sauer","year":"2021","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1093750","DOI":"10.3389\/fimmu.2023.1093750","article-title":"Preclinical evaluation of CD70-specific CAR T cells targeting acute myeloid leukemia","volume":"14","author":"Wu","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7641","DOI":"10.1073\/pnas.0502439102","article-title":"The activating NKG2D receptor assembles in the membrane with two signaling dimers into a hexameric structure","volume":"102","author":"Garrity","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1158\/2326-6066.CIR-15-0098","article-title":"NKG2D receptor and its ligands in host defense","volume":"3","author":"Lanier","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Deeren, D., Maertens, J., Lin, T., Beguin, Y., Demoulin, B., Fontaine, M., Sotiropoulou, P.A., Alcantar-Orozco, E., Breman, E., and Dheur, M.-S. (2020, January 5\u20138). First results from the dose escalation segment of the phase I clinical study evaluating Cyad-02, an optimized non gene-edited engineered NKG2D CAR T-cell product, in relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome patients. Proceedings of the 62nd Annual ASH Meeting, Virtual.","DOI":"10.1182\/blood-2020-139667"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1182\/blood.V98.6.1752","article-title":"The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: Analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials","volume":"6","author":"Kottaridis","year":"2001","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1182\/blood-2002-02-0492","article-title":"The roles of FLT3 in hematopoiesis and leukemia","volume":"5","author":"Gilliland","year":"2002","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1182\/blood.V97.8.2434","article-title":"Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies","volume":"8","author":"Yamamoto","year":"2001","journal-title":"Blood"},{"key":"ref_87","first-page":"1072","article-title":"Preclinical development of FLT3-redirected chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia","volume":"128","author":"Chien","year":"2016","journal-title":"Am. Soc. Hematol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13045-018-0603-7","article-title":"Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells","volume":"1","author":"Wang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/(SICI)1096-8652(199808)58:4<278::AID-AJH5>3.0.CO;2-N","article-title":"Biologic and clinical significance of CD7 expression in acute myeloid leukemia","volume":"4","author":"Saxena","year":"1998","journal-title":"Am. J. Hematol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1182\/blood-2017-01-761320","article-title":"CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies","volume":"130","author":"Srinivasan","year":"2017","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/(SICI)1097-0142(19990115)85:2<348::AID-CNCR12>3.0.CO;2-4","article-title":"Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia","volume":"2","author":"Ross","year":"1999","journal-title":"Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/79526","article-title":"Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia","volume":"6","author":"Molldrem","year":"2000","journal-title":"Nat. Med."},{"key":"ref_93","first-page":"985","article-title":"A novel TCR-like CAR with specificity for PR1\/HLA-A2 effectively targets myeloid leukemia in vitro when expressed in human adult peripheral blood and cord blood T cells","volume":"8","author":"Ma","year":"2016","journal-title":"Cyto-therapy"},{"key":"ref_94","first-page":"36","article-title":"Review of the Results of WT1 Peptide Vaccination Strategies for Myelodysplastic Syndromes and Acute Myeloid Leukemia from Nine Different Studies","volume":"6","author":"Jimenez","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_95","first-page":"55","article-title":"The post-transcriptional roles of WT1, a multifunctional zinc-finger protein","volume":"1","author":"Morrison","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1016\/j.ymthe.2018.08.001","article-title":"A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML","volume":"26","author":"John","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7379","DOI":"10.1182\/blood-2022-165339","article-title":"CD84: A Novel Target for CAR T-Cell Therapy for Acute Myeloid Leukemia","volume":"140","author":"Santos","year":"2022","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1182\/blood.2020009192","article-title":"Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia","volume":"138","author":"Jetani","year":"2021","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"10501","DOI":"10.1038\/ncomms10501","article-title":"Adaptive re-sistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints","volume":"7","author":"Koyama","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1182\/blood.2019002779","article-title":"Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia","volume":"135","author":"He","year":"2020","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1158\/2643-3230.BCD-20-0208","article-title":"NOT-Gated CD93 CAR T Cells Effectively Target AML with Minimized Endothelial Cross-Reactivity","volume":"2","author":"Richards","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41591-018-0036-4","article-title":"Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells","volume":"24","author":"Norelli","year":"2018","journal-title":"Nat. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41591-018-0041-7","article-title":"CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade","volume":"24","author":"Giavridis","year":"2018","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41577-021-00547-6","article-title":"Cytokine release syndrome and associated neurotoxicity in cancer im-munotherapy","volume":"22","author":"Morris","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5430","DOI":"10.1074\/jbc.AC119.007558","article-title":"Granulocyte\u2013macrophage colony-stimulating factor inactivation in CAR T-cells prevents monocyte-dependent release of key cytokine release syndrome mediators","volume":"14","author":"Sachdeva","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","article-title":"Chimeric antigen receptor T-cell therapy\u2014Assessment and management of toxicities","volume":"15","author":"Neelapu","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1038\/s41409-019-0487-3","article-title":"Early and late hematologic toxicity following CD19 CAR-T cells","volume":"10","author":"Fried","year":"2019","journal-title":"Bone Marrow Transplant."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1038\/s41409-019-0674-2","article-title":"Autologous hematopoietic stem cell infusion for sustained myelo-suppression after BCMA-CAR-T therapy in patient with relapsed myeloma","volume":"6","author":"Lin","year":"2020","journal-title":"Bone Marrow Transplant."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.bbmt.2020.04.025","article-title":"Feasibility and Safety of CD19 Chimeric Antigen Receptor T Cell Treatment for B Cell Lymphoma Relapse after Allogeneic Hematopoietic Stem Cell Transplantation","volume":"9","author":"Schubert","year":"2020","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1158\/2159-8290.CD-18-0442","article-title":"Tumor Antigen Escape from CAR T-cell Therapy","volume":"8","author":"Majzner","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4017","DOI":"10.1182\/blood-2014-12-580068","article-title":"CD19-targeted chimeric antigen receptor T-cell therapy for acute lym-phoblastic leukemia","volume":"125","author":"Maude","year":"2015","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1182\/blood-2018-99-117729","article-title":"Fully human bcma targeted chimeric antigen receptor T cells administered in a defined composition demon-strate potency at low doses in advanced stage high risk multiple myeloma","volume":"132","author":"Green","year":"2018","journal-title":"Blood"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1200\/JCO.2018.77.8084","article-title":"T Cells Genetically Modified to Express an Anti\u2013B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma","volume":"22","author":"Brudno","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1172\/JCI126397","article-title":"B cell maturation antigen\u2013specific CAR T cells are clinically active in multiple myeloma","volume":"6","author":"Cohen","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1038\/s41591-021-01436-0","article-title":"CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: A phase 1 trial","volume":"8","author":"Spiegel","year":"2021","journal-title":"Nat. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1038\/s41591-021-01497-1","article-title":"CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: A phase 1 trial","volume":"27","author":"Cordoba","year":"2021","journal-title":"Nat. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1158\/1078-0432.CCR-20-1457","article-title":"CD19-specific CAR T cells that express a PD-1\/CD28 chimeric switch-receptor are effective in patients with PD-L1-positive b-cell lymphoma","volume":"27","author":"Liu","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"7522","DOI":"10.1200\/JCO.2022.40.16_suppl.7522","article-title":"Phase 1\/2 study of anbalcabtagene autoleucel, novel anti-CD19 CAR-T cell therapy with dual silencing of PD-1 and TIGIT in relapsed or refractory large B-cell lymphoma","volume":"40","author":"Kim","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41571-019-0297-y","article-title":"Engineering strategies to overcome the current roadblocks in CAR T cell therapy","volume":"17","author":"Rafiq","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41573-019-0051-2","article-title":"\u2018Off-the-shelf\u2019 allogeneic CAR T cells: Development and challenges","volume":"19","author":"Depil","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1158\/0008-5472.CAN-14-3321","article-title":"Multiplex Genome-Edited T-cell Manufacturing Platform for \u201cOff-the-Shelf\u201d Adoptive T-cell Immunotherapies","volume":"75","author":"Poirot","year":"2015","journal-title":"Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/gt.2014.26","article-title":"TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer","volume":"21","author":"Berdien","year":"2014","journal-title":"Gene Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1182\/blood-2022-169928","article-title":"AMELI-01: A Phase I Trial of UCART123v1.2, an Anti-CD123 Allogeneic CAR-T Cell Product, in Adult Patients with Relapsed or Refractory (R\/R) CD123+ Acute Myeloid Leukemia (AML)","volume":"140","author":"Sallman","year":"2022","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/1\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:42:24Z","timestamp":1760132544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/1\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":125,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cancers16010042"],"URL":"https:\/\/doi.org\/10.3390\/cancers16010042","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]}}}