{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:06:03Z","timestamp":1784221563882,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"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>The treatment of acute myeloid leukemia (AML) remains challenging, largely due to high relapse rates following standard therapies. T-cell engagers (TCEs) offer a promising immunotherapeutic approach by redirecting T cells to recognize and kill AML cells. These therapeutic proteins bind CD3 to T cells and a tumor-associated antigen to AML cells, facilitating targeted immune activation. While CD33 and CD123 are the most commonly targeted AML antigens, others such as CD135, CD38, and CLEC12A\/CLL-1 are being evaluated in preclinical and clinical studies. In parallel, various TCE formats\u2014including BiTEs, DuoBodies, DARTs, and DARPin-based constructs\u2014have been developed to optimize pharmacokinetics, stability, and immune engagement. Despite the growing number of TCEs entering clinical evaluation, none have advanced beyond early Phase (I\/II) trials, primarily due to the lack of optimal target antigens and challenges in balancing antileukemic activity with the risks of immune-related toxicities such as cytokine release syndrome (CRS). This review aims to summarize the current landscape of TCE development in AML, highlighting key targets, formats, and challenges.<\/jats:p>","DOI":"10.3390\/cancers17193246","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T08:05:36Z","timestamp":1759824336000},"page":"3246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["T-Cell Engagers in Acute Myeloid Leukemia: Molecular Targets, Structure, and Therapeutic Challenges"],"prefix":"10.3390","volume":"17","author":[{"given":"Hunter","family":"Daws","sequence":"first","affiliation":[{"name":"Vanadro Drug Development Consulting, West Des Moines, IA 50266, USA"},{"name":"College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Gallinero","sequence":"additional","affiliation":[{"name":"Vanadro Drug Development Consulting, West Des Moines, IA 50266, USA"},{"name":"College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1354-4563","authenticated-orcid":false,"given":"Amanda","family":"Singh","sequence":"additional","affiliation":[{"name":"Vanadro Drug Development Consulting, West Des Moines, IA 50266, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanela","family":"Bilic","sequence":"additional","affiliation":[{"name":"Vanadro Drug Development Consulting, West Des Moines, IA 50266, USA"},{"name":"College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000536152","article-title":"Pathophysiology of Acute Myeloid Leukemia","volume":"147","author":"Wachter","year":"2024","journal-title":"Acta Haematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11864-020-00765-5","article-title":"Treatment of Relapsed Acute Myeloid Leukemia","volume":"21","author":"Thol","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1002\/jcph.445","article-title":"Clinical pharmacology of bispecific antibody constructs","volume":"55","author":"Rathi","year":"2015","journal-title":"J. Clin. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nri2155","article-title":"FcRn: The neonatal Fc receptor comes of age","volume":"7","author":"Roopenian","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s40262-016-0405-4","article-title":"Blinatumomab, a Bispecific T-cell Engager (BiTE(\u00ae)) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications","volume":"55","author":"Zhu","year":"2016","journal-title":"Clin. Pharmacokinet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1002\/cncr.32909","article-title":"The BiTE (bispecific T-cell engager) platform: Development and future potential of a targeted immuno-oncology therapy across tumor types","volume":"126","author":"Einsele","year":"2020","journal-title":"Cancer"},{"key":"ref_7","first-page":"2815","article-title":"Generation of a Half-Life Extended Anti-CD19 BiTE\u00ae Antibody Construct Compatible with Once-Weekly Dosing for Treatment of CD19-Positive Malignancies","volume":"130","author":"Lorenczewski","year":"2017","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cech, P., Sk\u00f3rka, K., Dziki, L., and Giannopoulos, K. (2024). T-Cell Engagers-The Structure and Functional Principle and Application in Hematological Malignancies. Cancers, 16.","DOI":"10.3390\/cancers16081580"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/imr.13379","article-title":"Living in LALA land? Forty years of attenuating Fc effector functions","volume":"328","author":"Hale","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5829","DOI":"10.1158\/1078-0432.CCR-16-0350","article-title":"Characterization of CD33\/CD3 Tetravalent Bispecific Tandem Diabodies (TandAbs) for the Treatment of Acute Myeloid Leukemia","volume":"22","author":"Reusch","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"962","DOI":"10.4161\/mabs.26233","article-title":"Production of stable bispecific IgG1 by controlled Fab-arm exchange: Scalability from bench to large-scale manufacturing by application of standard approaches","volume":"5","author":"Gramer","year":"2013","journal-title":"MAbs."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"42","DOI":"10.32607\/20758251-2019-11-4-42-53","article-title":"DARPins: Promising Scaffolds for Theranostics","volume":"11","author":"Shilova","year":"2019","journal-title":"Acta Naturae"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1182\/blood-2013-08-523548","article-title":"CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330","volume":"123","author":"Krupka","year":"2014","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Subklewe, M., Stein, A., Walter, R.B., Bhatia, R., Wei, A.H., Ritchie, D., Buecklein, V., Vachhani, P., Dai, T., and Hindoyan, A. (2020). Updated Results from a Phase 1 First-in-Human Dose Escalation Study of AMG 673, a Novel Anti-CD33\/CD3 BiTE\u00ae (Bispecific T-cell Engager) in Patients with Relapsed\/Refractory Acute Myeloid Leukemia, European Hematology Association.","DOI":"10.1182\/blood-2019-127977"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e13742","DOI":"10.1111\/cts.13742","article-title":"First-in-human study of JNJ-67571244, a CD33 \u00d7 CD3 bispecific antibody, in relapsed\/refractory acute myeloid leukemia and myelodysplastic syndrome","volume":"17","author":"Narayan","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Eissenberg, L.G., Ritchey, J.K., Rettig, M.P., Patel, D.A., Vij, K., Gao, F., Smith, V., Han, T.H., and DiPersio, J.F. (2024). Control of acute myeloid leukemia and generation of immune memory in vivo using AMV564, a bivalent bispecific CD33 \u00d7 CD3 T cell engager. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0300174"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1182\/blood-2019-129042","article-title":"Phase 1 First-in-Human Trial of AMV564, a Bivalent Bispecific (2:2) CD33\/CD3 T-Cell Engager, in Patients with Relapsed\/Refractory Acute Myeloid Leukemia (AML)","volume":"134","author":"Westervelt","year":"2019","journal-title":"Blood"},{"key":"ref_18","unstructured":"Bories, P., Gri\u0161kevi\u010dius, L., Jongen-Lavrencic, M., Pabst, T., De Leeuw, D., Huls, G., Pigneux, A., Boissel, N., Boettcher, S., and Dymkowska, M. (2025). Updated Results from the Ongoing Phase 1\/2a Study of MP0533, a Tetra-Specific Designed Ankyrin Repeat Protein (DARPin; CD33 x CD123 x CD70 x CD3), in Patients with Relapsed\/Refractory AML or MDS\/AML, EHA."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289ra82","DOI":"10.1126\/scitranslmed.aaa5693","article-title":"A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: Preclinical activity and safety in nonhuman primates","volume":"7","author":"Chichili","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1182\/blood-2021-153192","article-title":"Combinatorial Anti-Tumor Activity in Animal Models of a Novel CD123 x CD3 Bispecific DART\u00ae Molecule (MGD024) with Cytarabine, Venetoclax or Azacitidine Supports Combination Therapy in Acute Myeloid Leukemia","volume":"138","author":"Alderson","year":"2021","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ymeth.2018.10.006","article-title":"A robust heterodimeric Fc platform engineered for efficient development of bispecific antibodies of multiple formats","volume":"154","author":"Moore","year":"2019","journal-title":"Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1182\/blood.V128.22.2875.2875","article-title":"Ex Vivo Activity Profile of the CD123xCD3 Duobody\u00ae Antibody JNJ-63709178 Against Primary Acute Myeloid Leukemia Bone Marrow Samples","volume":"128","author":"Forslund","year":"2016","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1158\/1538-7445.AM2018-1786","article-title":"Abstract 1786: APVO436, a bispecific anti-CD123 x anti-CD3 ADAPTIR\u2122 molecule for redirected T-cell cytotoxicity, induces potent T-cell activation, proliferation and cytotoxicity with limited cytokine release","volume":"78","author":"Comeau","year":"2018","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1945803","DOI":"10.1080\/2162402X.2021.1945803","article-title":"Pre-clinical development of a novel CD3-CD123 bispecific T-cell engager using cross-over dual-variable domain (CODV) format for acute myeloid leukemia (AML) treatment","volume":"10","author":"Bonnevaux","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1182\/blood.V126.23.325.325","article-title":"Preclinical Evaluation of MCLA117, a CLEC12AxCD3 Bispecific Antibody Efficiently Targeting a Novel Leukemic Stem Cell Associated Antigen in AML","volume":"126","author":"Doornbos","year":"2015","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1158\/1535-7163.MCT-19-1093","article-title":"Characterization of a Novel FLT3 BiTE Molecule for the Treatment of Acute Myeloid Leukemia","volume":"19","author":"Brauchle","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e003882","DOI":"10.1136\/jitc-2021-003882","article-title":"A novel IgG-based FLT3xCD3 bispecific antibody for the treatment of AML and B-ALL","volume":"10","author":"Mehta","year":"2022","journal-title":"J. Immunother. Cancer."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1182\/blood-2023-187721","article-title":"A Phase 1 Study of CD38-Bispecific Antibody (XmAb18968) for Patients with CD38 Expressing Relapsed\/Refractory Acute Myeloid Leukemia","volume":"142","author":"Leonard","year":"2023","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Dreyzin, A., Holtzman, N.G., and Bonifant, C.L. (2025). CD123-targeting immunotherapeutic approaches in acute myeloid leukaemia. Br. J. Haematol., 1\u201314.","DOI":"10.1111\/bjh.70019"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/35102167","article-title":"Stem cells, cancer, and cancer stem cells","volume":"414","author":"Reya","year":"2001","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1038\/bcj.2014.39","article-title":"Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia","volume":"4","author":"Ehninger","year":"2014","journal-title":"Blood Cancer J."},{"key":"ref_32","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, 12.","DOI":"10.3390\/cancers12113087"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1038\/s41375-021-01253-x","article-title":"T-cell-based immunotherapy of acute myeloid leukemia: Current concepts and future developments","volume":"35","author":"Daver","year":"2021","journal-title":"Leukemia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11899-018-0472-8","article-title":"Bispecific Antibodies for the Treatment of Acute Myeloid Leukemia","volume":"13","author":"Guy","year":"2018","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.blre.2014.04.001","article-title":"The past and future of CD33 as therapeutic target in acute myeloid leukemia","volume":"28","author":"Laszlo","year":"2014","journal-title":"Blood Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.exphem.2017.06.007","article-title":"Unlocking the potential of anti-CD33 therapy in adult and childhood acute myeloid leukemia","volume":"54","author":"Laing","year":"2017","journal-title":"Exp. Hematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1189\/jlb.0205096","article-title":"A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: Two isoforms of CD33 are generated by alternative splicing","volume":"79","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1182\/blood-2013-09-527044","article-title":"Cellular determinants for preclinical activity of a novel CD33\/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML","volume":"123","author":"Laszlo","year":"2014","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1080\/10428194.2024.2346755","article-title":"Safety and tolerability of AMG 330 in adults with relapsed\/refractory AML: A phase 1a dose-escalation study","volume":"65","author":"Ravandi","year":"2024","journal-title":"Leuk. Lymphoma."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1182\/blood-2019-127977","article-title":"Preliminary Results from a Phase 1 First-in-Human Study of AMG 673, a Novel Half-Life Extended (HLE) Anti-CD33\/CD3 BiTE\u00ae (Bispecific T-Cell Engager) in Patients with Relapsed\/Refractory (R\/R) Acute Myeloid Leukemia (AML)","volume":"134","author":"Subklewe","year":"2019","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1182\/bloodadvances.2019001188","article-title":"A novel C2 domain binding CD33xCD3 bispecific antibody with potent T-cell redirection activity against acute myeloid leukemia","volume":"4","author":"Diem","year":"2020","journal-title":"Blood Adv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1200\/JCO.2021.39.15_suppl.2555","article-title":"Results of a phase 1 dose-escalation study of AMV564, a novel T-cell engager, alone and in combination with pembrolizumab in patients with relapsed\/refractory solid tumors","volume":"39","author":"Mettu","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1182\/blood-2024-199211","article-title":"MP0533 (CD33 x CD123 x CD70 x CD3), a Tetra-Specific CD3-Engaging Darpin for the Treatment of Patients with Relapsed\/Refractory AML or MDS\/AML: Results of an Ongoing Phase 1\/2a Study","volume":"144","author":"Pabst","year":"2024","journal-title":"Blood"},{"key":"ref_44","first-page":"1261","article-title":"Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies","volume":"86","author":"Carnicer","year":"2001","journal-title":"Haematologica"},{"key":"ref_45","first-page":"200","article-title":"Recombinant human IL-3 and G-CSF act synergistically in stimulating the growth of acute myeloid leukemia cells","volume":"3","author":"Lafage","year":"1989","journal-title":"Leukemia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e673","DOI":"10.1016\/j.clml.2020.05.004","article-title":"A Real-world Perspective of CD123 Expression in Acute Leukemia as Promising Biomarker to Predict Treatment Outcome in B-ALL and AML","volume":"20","author":"Das","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1182\/blood-2014-05-575704","article-title":"Targeting CD123 in acute myeloid leukemia using a T-cell-directed dual-affinity retargeting platform","volume":"127","author":"Rettig","year":"2016","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1182\/blood.2020007732","article-title":"Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia","volume":"137","author":"Uy","year":"2021","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11753","DOI":"10.1182\/blood-2022-159524","article-title":"A Phase 1, First-in-Human, Dose-Escalation Study of MGD024, a CD123 x CD3 Bispecific Dart\u00ae Molecule, in Patients with Relapsed or Refractory CD123-Positive (+) Hematologic Malignancies","volume":"140","author":"Winer","year":"2022","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1182\/blood.V124.21.2316.2316","article-title":"Immunotherapy with Long-Lived Anti-CD123 \u00d7 Anti-CD3 Bispecific Antibodies Stimulates Potent T Cell-Mediated Killing of Human AML Cell Lines and of CD123+ Cells in Monkeys: A Potential Therapy for Acute Myelogenous Leukemia","volume":"124","author":"Chu","year":"2014","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6492","DOI":"10.1182\/bloodadvances.2023010956","article-title":"Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed\/refractory acute myeloid leukemia","volume":"7","author":"Ravandi","year":"2023","journal-title":"Blood Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/cts.13467","article-title":"First-in-human study of JNJ-63709178, a CD123\/CD3 targeting antibody, in relapsed\/refractory acute myeloid leukemia","volume":"16","author":"Boyiadzis","year":"2023","journal-title":"Clin. Transl. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Uckun, F.M., Lin, T.L., Mims, A.S., Patel, P., Lee, C., Shahidzadeh, A., Shami, P.J., Cull, E., Cogle, C.R., and Watts, J. (2021). A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed\/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Cancers, 13.","DOI":"10.3390\/cancers13164113"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1158\/1538-7445.AM2022-2909","article-title":"CD123-CODV-TCE bispecific T-cell engager for acute myeloid leukemia (AML): Activity on primary AML and safety in non-human primates","volume":"82","author":"Bonnevaux","year":"2022","journal-title":"Cancer Res."},{"key":"ref_55","first-page":"238","article-title":"Human FLT3\/FLK2 receptor tyrosine kinase is expressed at the surface of normal and malignant hematopoietic cells","volume":"10","author":"Rosnet","year":"1996","journal-title":"Leukemia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1182\/blood.V87.3.1089.bloodjournal8731089","article-title":"Expression of the hematopoietic growth factor receptor FLT3 (STK-1\/Flk2) in human leukemias","volume":"87","author":"Carow","year":"1996","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tsapogas, P., Mooney, C., Brown, G., and Rolink, A. (2017). The cytokine Flt3-ligand in normal and malignant hematopoiesis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061115"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.blre.2018.10.003","article-title":"Prognostic and therapeutic role of CLEC12A in acute myeloid leukemia","volume":"34","author":"Morsink","year":"2019","journal-title":"Blood Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1182\/blood-2007-03-083048","article-title":"The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells","volume":"110","author":"Kelder","year":"2007","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1158\/1078-0432.CCR-18-0333","article-title":"An Anti-CLL-1 Antibody-Drug Conjugate for the Treatment of Acute Myeloid Leukemia","volume":"25","author":"Zheng","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1182\/bloodadvances.2018020107","article-title":"CLT030, a leukemic stem cell-targeting CLL1 antibody-drug conjugate for treatment of acute myeloid leukemia","volume":"2","author":"Jiang","year":"2018","journal-title":"Blood Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1080\/14712598.2019.1623200","article-title":"MCLA-117, a CLEC12AxCD3 bispecific antibody targeting a leukaemic stem cell antigen, induces T cell-mediated AML blast lysis","volume":"19","author":"Hangalapura","year":"2019","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_63","unstructured":"Mascarenhas, J., Cortes, J., Huls, G., Venditti, A., Breems, D., De Botton, S., DeAngelo, D.J., van de Loosdrecht, A., Jongen-Lavrencic, M., and Borthakur, G. (2020). Update from the Ongoing Phase 1 Multinational Study of MCLA-117, a Bispecific CLEC12A X CD3 T-Cell Engager, in Patients with Acute Myelogenous Leukemia, European Hematology Association."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1007783","DOI":"10.3389\/fonc.2022.1007783","article-title":"Targeting CD38 for acute leukemia","volume":"12","author":"Zhong","year":"2022","journal-title":"Front Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0145-2126(99)00147-2","article-title":"Increased CD38 expression is associated with favorable prognosis in adult acute leukemia","volume":"24","author":"Keyhani","year":"2000","journal-title":"Leuk. Res."},{"key":"ref_66","first-page":"1639","article-title":"Analysis of immunophenotypes and expressions of non-myeloid antigens in acute myeloid leukemia","volume":"40","author":"Wang","year":"2020","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1182\/blood.2023021570","article-title":"A CD38-directed, single-chain T-cell engager targets leukemia stem cells through IFN-\u03b3-induced CD38 expression","volume":"143","author":"Murtadha","year":"2024","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"717","DOI":"10.6004\/jadpro.2022.13.7.8","article-title":"Tebentafusp-tebn: A Novel Bispecific T-Cell Engager for Metastatic Uveal Melanoma","volume":"13","author":"Hua","year":"2022","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13045-024-01586-x","article-title":"IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells","volume":"17","author":"Zhang","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1182\/blood-2012-09-458935","article-title":"Selective killing of candidate AML stem cells by antibody targeting of IL1RAP","volume":"121","author":"Askmyr","year":"2013","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104200","DOI":"10.1016\/j.critrevonc.2023.104200","article-title":"Interleukin-1 receptor accessory protein (IL-1RAP): A magic bullet candidate for immunotherapy of human malignancies","volume":"193","author":"Shahba","year":"2024","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1182\/blood-2023-185405","article-title":"IL1RAP-Specific T Cell Engager (TCE) Antibody Efficiently Depletes Acute Myeloid Leukemia (AML) Leukemic Stem Cells (LSCs)","volume":"142","author":"Zhang","year":"2023","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1158\/1535-7163.MCT-22-0770","article-title":"ABBV-184: A Novel Survivin-specific TCR\/CD3 Bispecific T-cell Engager is Active against Both Solid Tumor and Hematologic Malignancies","volume":"22","author":"Chervin","year":"2023","journal-title":"Mol. Cancer Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1182\/blood-2012-02-409888","article-title":"Survivin is highly expressed in CD34(+)38(-) leukemic stem\/progenitor cells and predicts poor clinical outcomes in AML","volume":"120","author":"Carter","year":"2012","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1080\/14737140.2024.2373888","article-title":"First-in-human clinical trial results with ABBV-184, a first-in-class T-cell receptor\/anti-CD3 bispecific protein, in adults with previously treated AML or NSCLC","volume":"24","author":"Peterlin","year":"2024","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/blood-2024-201699","article-title":"CBX250 Is a Novel Cathepsin G Peptide-HLA-Targeting T Cell Engager That Exhibits High Tumor Antigen Selectivity and Potent Antileukemic Activity In Vivo","volume":"144","author":"Lee","year":"2024","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1158\/1078-0432.CCR-12-2753","article-title":"A novel HLA-A*0201 restricted peptide derived from cathepsin G is an effective immunotherapeutic target in acute myeloid leukemia","volume":"19","author":"Zhang","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Albayrak, G., Wan, P.K., Fisher, K., and Seymour, L.W. (2025). T cell engagers: Expanding horizons in oncology and beyond. Br. J. Cancer., 1\u20139.","DOI":"10.1038\/s41416-025-03125-y"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/19\/3246\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:49:51Z","timestamp":1760035791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/19\/3246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":78,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["cancers17193246"],"URL":"https:\/\/doi.org\/10.3390\/cancers17193246","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]}}}