{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:40:43Z","timestamp":1784043643856,"version":"3.55.0"},"reference-count":157,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["JR22\/00041"],"award-info":[{"award-number":["JR22\/00041"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies, such as antibody-based therapy, checkpoint inhibitors, and chimeric antigen receptor strategies, successfully tested in other hematologic malignancies, were very high. The inherent characteristics of AML blasts hampered the development of these treatments, and the path of immunotherapy in AML has been bumpy. Herein, we provide a detailed review of potential antigenic targets, available data from pre-clinical and clinical trials, and future directions of immunotherapies in AML.<\/jats:p>","DOI":"10.3390\/bioengineering10101228","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T11:53:56Z","timestamp":1697802836000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-0663","authenticated-orcid":false,"given":"Luca","family":"Guarnera","sequence":"first","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-7847","authenticated-orcid":false,"given":"Carlos","family":"Bravo-Perez","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, University of Murcia, IMIB-Pascual Parrilla, CIBERER\u2014Instituto de Salud Carlos III, 30005 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-1509","authenticated-orcid":false,"given":"Valeria","family":"Visconte","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1182\/blood-2002-04-1199","article-title":"The World Health Organization (WHO) classification of the myeloid neoplasms","volume":"100","author":"Vardiman","year":"2002","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1300874","article-title":"Retinoic acid and arsenic trioxide for acute promyelocytic leukemia","volume":"369","author":"Avvisati","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"871590","DOI":"10.3389\/fonc.2022.871590","article-title":"Atypical Rearrangements in APL-Like Acute Myeloid Leukemias: Molecular Characterization and Prognosis","volume":"12","author":"Guarnera","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S1470-2045(09)70003-8","article-title":"Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: A randomised, open-label, phase III study","volume":"10","author":"Fenaux","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood-2018-08-868752","article-title":"Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia","volume":"133","author":"DiNardo","year":"2019","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/S0140-6736(12)60485-1","article-title":"Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): A randomised, open-label, phase 3 study","volume":"379","author":"Castaigne","year":"2012","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3389\/fonc.2019.00655","article-title":"MRD in AML: The Role of New Techniques","volume":"9","author":"Voso","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jtct.2022.12.013","article-title":"An Analysis of the Worldwide Utilization of Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia","volume":"29","author":"Tokaz","year":"2023","journal-title":"Transplant. Cell Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.clml.2021.05.016","article-title":"Acute Myeloid Leukemia: Historical Perspective and Progress in Research and Therapy over 5 Decades","volume":"21","author":"Kantarjian","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_11","first-page":"233","article-title":"Graft-versus-leukemia following bone marrow transplantation","volume":"2","author":"Butturini","year":"1987","journal-title":"Bone Marrow Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Guarnera, L., Santinelli, E., Galossi, E., Cristiano, A., Fabiani, E., Falconi, G., and Voso, M.T. (2023). Microenvironment in Acute Myeloid Leukemia: Focus on senescence mechanisms, therapeutic interactions and future directions. Exp. Hematol.","DOI":"10.1016\/j.exphem.2023.09.005"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature10160","article-title":"In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche","volume":"474","author":"Fujisaki","year":"2011","journal-title":"Nature"},{"key":"ref_14","first-page":"e1","article-title":"Outcomes After Donor Lymphocyte Infusion in Patients with Hematological Malignancies: Donor Characteristics Matter","volume":"28","author":"Snowden","year":"2022","journal-title":"Transplant. Cell. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1182\/blood-2009-03-210393","article-title":"Immunomodulatory effect of 5-azacytidine (5-azaC): Potential role in the transplantation setting","volume":"115","author":"Blanco","year":"2010","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.4049\/jimmunol.1502399","article-title":"Azacitidine Mitigates Graft-versus-Host Disease via Differential Effects on the Proliferation of T Effectors and Natural Regulatory T Cells In Vivo","volume":"198","author":"Cooper","year":"2017","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41408-022-00615-7","article-title":"Azacitidine-induced reconstitution of the bone marrow T cell repertoire is associated with superior survival in AML patients","volume":"12","author":"Grimm","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/nrd3031","article-title":"Immunomodulatory effects of deacetylase inhibitors: Therapeutic targeting of FOXP3+ regulatory T cells","volume":"8","author":"Wang","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"690901","DOI":"10.5402\/2012\/690901","article-title":"Regulation of immune responses by histone deacetylase inhibitors","volume":"2012","author":"Licciardi","year":"2012","journal-title":"ISRN Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"641910","DOI":"10.3389\/fimmu.2021.641910","article-title":"Immunomodulatory Effects of Histone Deacetylation Inhibitors in Graft-vs.-Host Disease After Allogeneic Stem Cell Transplantation","volume":"12","author":"Xu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nm.4484","article-title":"Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells","volume":"24","author":"Mathew","year":"2018","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S1658-3876(08)50011-2","article-title":"Stabilization of acute myeloid leukemia with a dendritic cell vaccine","volume":"1","author":"Massumoto","year":"2008","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_23","first-page":"855","article-title":"Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts","volume":"28","author":"Li","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.exphem.2011.01.001","article-title":"Cross-priming of CD8(+) T cells in vivo by dendritic cells pulsed with autologous apoptotic leukemic cells in immunotherapy for elderly patients with acute myeloid leukemia","volume":"39","author":"Kitawaki","year":"2011","journal-title":"Exp. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1177\/147323001204000405","article-title":"Autologous dendritic cells combined with cytokine-induced killer cells synergize low-dose chemotherapy in elderly patients with acute myeloid leukaemia","volume":"40","author":"Dong","year":"2012","journal-title":"J. Int. Med. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"368ra171","DOI":"10.1126\/scitranslmed.aag1298","article-title":"Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions","volume":"8","author":"Rosenblatt","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1182\/blood-2021-148333","article-title":"Treatment with an Allogeneic Leukemia-Derived Dendritic Cell Vaccine in AML Patients Shows MRD Conversion and Improved Survival","volume":"138","author":"Cloos","year":"2021","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1111\/j.1365-2141.2010.08490.x","article-title":"A phase I\/IIa clinical trial of immunotherapy for elderly patients with acute myeloid leukaemia using dendritic cells co-pulsed with WT1 peptide and zoledronate","volume":"153","author":"Kitawaki","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1016\/j.bbmt.2016.08.028","article-title":"Induction of Immune Response after Allogeneic Wilms\u2019 Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse","volume":"22","author":"Shah","year":"2016","journal-title":"Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Barbullushi, K., Rampi, N., Serpenti, F., Scium\u00e8, M., Fabris, S., De Roberto, P., and Fracchiolla, N.S. (2022). Vaccination Therapy for Acute Myeloid Leukemia: Where Do We Stand?. Cancers, 14.","DOI":"10.3390\/cancers14122994"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rautenberg, C., Germing, U., Haas, R., Kobbe, G., and Schroeder, T. (2019). Relapse of Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation: Prevention, Detection, and Treatment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010228"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/icb.2014.93","article-title":"Bispecific T-cell engagers for cancer immunotherapy","volume":"93","author":"Huehls","year":"2015","journal-title":"Immunol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1111\/jcpt.13741","article-title":"The pharmacology of blinatumomab: State of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials","volume":"47","author":"Mocquot","year":"2022","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"626616","DOI":"10.3389\/fimmu.2021.626616","article-title":"Bispecific Antibodies: From Research to Clinical Application","volume":"12","author":"Ma","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100870","DOI":"10.1016\/j.mam.2020.100870","article-title":"NK cells and ILCs in tumor immunotherapy","volume":"80","author":"Sivori","year":"2021","journal-title":"Mol. Asp. Med."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/myc.13411","article-title":"Pneumocystis jirovecii pneumonia in patients with previously untreated acute myeloid leukaemia","volume":"65","author":"Paterno","year":"2022","journal-title":"Mycoses"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2023013","DOI":"10.4084\/MJHID.2023.013","article-title":"Fever of Unknown Origin and Multidrug Resistant Organism Colonization in AML Patients","volume":"15","author":"Guarnera","year":"2023","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1007\/s00277-018-3341-6","article-title":"Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria","volume":"97","author":"Cattaneo","year":"2018","journal-title":"Ann. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.leukres.2006.07.005","article-title":"Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): An overview from the research on adverse drug events and reports (RADAR) project","volume":"31","author":"McKoy","year":"2007","journal-title":"Leuk. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Subklewe","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S1470-2045(14)70281-5","article-title":"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","volume":"15","author":"Hills","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1056\/NEJMoa1815105","article-title":"Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm","volume":"380","author":"Pemmaraju","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1182\/blood-2021-147486","article-title":"Safety and Efficacy of Combining Tagraxofusp (SL-401) with Azacitidine or Azacitidine and Venetoclax in a Phase 1b Study for CD123 Positive AML, MDS, or BPDCN","volume":"138","author":"Lane","year":"2021","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11749","DOI":"10.1182\/blood-2022-170738","article-title":"Phase II Study of Tagraxofusp in Newly Diagnosed Secondary Acute Myeloid Leukemia (S-AML) after Previous Exposure to Hypomethylating Agents (TAGALONG Study)","volume":"140","author":"Green","year":"2022","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1182\/blood-2018-99-117085","article-title":"Phase 1 Cohort Expansion of Flotetuzumab, a CD123\u00d7CD3 Bispecific Dart\u00ae Protein in Patients with Relapsed\/Refractory Acute Myeloid Leukemia (AML)","volume":"132","author":"Uy","year":"2018","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":"25","DOI":"10.1182\/blood-2018-99-109762","article-title":"A Phase 1 First-in-Human Study of AMG 330, an Anti-CD33 Bispecific T-Cell Engager (BiTE\u00ae) Antibody Construct, in Relapsed\/Refractory Acute Myeloid Leukemia (R\/R AML)","volume":"132","author":"Ravandi","year":"2018","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7508","DOI":"10.1200\/JCO.2020.38.15_suppl.7508","article-title":"Updated results from phase I dose-escalation study of AMG 330, a bispecific T-cell engager molecule, in patients with relapsed\/refractory acute myeloid leukemia (R\/R AML)","volume":"38","author":"Ravandi","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_51","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_52","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1182\/blood-2020-134746","article-title":"Complete Responses in Relapsed\/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of Vibecotamab (XmAb14045), a CD123 x CD3 T Cell-Engaging Bispecific Antibody; Initial Results of a Phase 1 Study","volume":"136","author":"Ravandi","year":"2020","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"TPS7076","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS7076","article-title":"A phase II study of vibecotamab, a CD3-CD123 bispecific T-cell engaging antibody, for MRD-positive AML and MDS after hypomethylating agent failure","volume":"41","author":"Short","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"6204","DOI":"10.1182\/blood-2022-167468","article-title":"Updated Results from a Phase 1 Study of APVO436, a Novel Bispecific Anti-CD123 x Anti-CD3 AdaptirTM Molecule, in Relapsed\/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome","volume":"140","author":"Watts","year":"2022","journal-title":"Blood"},{"key":"ref_56","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_57","unstructured":"Mascarenhas, J., Cortes, J., Huls, G., Venditti, A., Breems, D., De Botton, S., Deangelo, D., van de Loosdrecht, A., Jongen-Lavrencic, M., and Borthakur, G. (2020). Update from the Ongoing Phase I Multinational Study of MCLA-117, a Bispecific CLEC12A X CD3 T-Cell Engager, in Patients (Pts) with Acute Myelogenous Leukemia (AML), European Hematology Association."},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1158\/1078-0432.CCR-13-0505","article-title":"Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 x 33 bispecific killer cell engager and ADAM17 inhibition","volume":"19","author":"Wiernik","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1182\/blood-2013-10-533398","article-title":"CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets","volume":"123","author":"Gleason","year":"2014","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1007\/s00262-021-03008-0","article-title":"CD16xCD33 Bispecific Killer Cell Engager (BiKE) as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL","volume":"70","author":"Reusing","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_62","first-page":"7","article-title":"GTB-3550 TriKETM for the Treatment of High-Risk Myelodysplastic Syndromes (MDS) and Refractory\/Relapsed Acute Myeloid Leukemia (AML) Safely Drives Natural Killer (NK) Cell Proliferation at Initial dose Cohorts","volume":"136","author":"Erica","year":"2020","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Felices, M., Warlick, E., Juckett, M., Weisdorf, D., Vallera, D., Miller, S., Wangen, R., Lewis, D., Knox, J., and Schroeder, M. (2021). GTB-3550 tri-specific killer engager TriKETM drives NK cells expansion and cytotoxicity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients. J. Immunother. Cancer, 9.","DOI":"10.1136\/jitc-2021-SITC2021.444"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hughes-Parry, H.E., Cross, R.S., and Jenkins, M.R. (2019). The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010204"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ahmad, U., Khan, Z., Ualiyeva, D., Amissah, O.B., Noor, Z., Khan, A., Zaman, N., Khan, M., Khan, A., and Ali, B. (2022). Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review. Adv. Cancer Biol.-Metastasis, 4.","DOI":"10.1016\/j.adcanc.2022.100035"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Tang, H.K.C., Wang, B., Tan, H.X., Sarwar, M.A., Baraka, B., Shafiq, T., and Rao, A.R. (2023). CAR T-Cell Therapy for Cancer: Latest Updates and Challenges, with a Focus on B-Lymphoid Malignancies and Selected Solid Tumours. Cells, 12.","DOI":"10.3390\/cells12121586"},{"key":"ref_67","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_68","doi-asserted-by":"crossref","unstructured":"Wu, Z., Zhang, H., Wu, M., Peng, G., He, Y., Wan, N., and Zeng, Y. (2021). Targeting the NKG2D\/NKG2D-L axis in acute myeloid leukemia. Biomed. Pharmacother., 137.","DOI":"10.1016\/j.biopha.2021.111299"},{"key":"ref_69","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_70","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":"35","author":"Tambaro","year":"2021","journal-title":"Leukemia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1182\/blood-2021-150193","article-title":"Targeted Therapy in CD38 + Acute Myeloid Leukemia","volume":"138","author":"Hu","year":"2021","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4418","DOI":"10.1182\/bloodadvances.2022007059","article-title":"CD38 as a pan-hematologic target for chimeric antigen receptor T cells","volume":"7","author":"Diorio","year":"2023","journal-title":"Blood Adv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10313","DOI":"10.1182\/blood-2022-169142","article-title":"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","volume":"140","author":"Sallman","year":"2022","journal-title":"Blood"},{"key":"ref_74","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"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1182\/blood-2022-170201","article-title":"Safety and Anti-Leukemic Activity of CD123-CAR T Cells in Pediatric Patients with AML: Preliminary Results from a Phase 1 Trial","volume":"140","author":"Naik","year":"2022","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3389\/fonc.2020.00685","article-title":"Successful Anti-CLL1 CAR T-Cell Therapy in Secondary Acute Myeloid Leukemia","volume":"10","author":"Zhang","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_77","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":"15","author":"Jin","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"10000","DOI":"10.1200\/JCO.2021.39.15_suppl.10000","article-title":"The efficacy and safety of anti-CLL1 based CAR-T cells in children with relapsed or refractory acute myeloid leukemia: A multicenter interim analysis","volume":"39","author":"Zhang","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1038\/s41375-022-01703-0","article-title":"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","volume":"36","author":"Zhang","year":"2022","journal-title":"Leukemia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9655","DOI":"10.1002\/cam4.5916","article-title":"Anti-CLL1-based CAR T-cells with 4-1-BB or CD28\/CD27 stimulatory domains in treating childhood refractory\/relapsed acute myeloid leukemia","volume":"12","author":"Pei","year":"2023","journal-title":"Cancer Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7450","DOI":"10.1182\/blood-2022-170712","article-title":"Off-the-Shelf CD33 CAR-NK Cell Therapy for Relapse\/Refractory AML: First-in-Human, Phase I Trial","volume":"140","author":"Huang","year":"2022","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1186\/s12967-022-03797-7","article-title":"Naturally selected CD7 CAR-T therapy without genetic editing demonstrates significant antitumour efficacy against relapsed and refractory acute myeloid leukaemia (R\/R-AML)","volume":"20","author":"Lu","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.3109\/10428194.2012.754096","article-title":"CD19 expression in acute leukemia is not restricted to the cytogenetically aberrant populations","volume":"54","author":"Francis","year":"2013","journal-title":"Leuk. Lymphoma"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e1043","DOI":"10.1002\/ctm2.1043","article-title":"CD44v6 chimeric antigen receptor T cell specificity towards AML with FLT3 or DNMT3A mutations","volume":"12","author":"Tang","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_85","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_86","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3324\/haematol.2022.281456","article-title":"Potent preclinical activity of FLT3-directed chimeric antigen receptor T-cell immunotherapy against FLT3- mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia","volume":"108","author":"Niswander","year":"2023","journal-title":"Haematologica"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Shao, R., Li, Z., Xin, H., Jiang, S., Zhu, Y., Liu, J., Huang, R., Xu, K., and Shi, X. (2023). Biomarkers as targets for CAR-T\/NK cell therapy in AML. Biomark. Res., 11.","DOI":"10.1186\/s40364-023-00501-9"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1158\/1078-0432.CCR-20-2540","article-title":"Preclinical Evaluation of B7-H3-specific Chimeric Antigen Receptor T Cells for the Treatment of Acute Myeloid Leukemia","volume":"27","author":"Lichtman","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.intimp.2018.06.001","article-title":"Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors","volume":"62","author":"Hargadon","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Kuzume, A., Chi, S., Yamauchi, N., and Minami, Y. (2020). Immune-Checkpoint Blockade Therapy in Lymphoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155456"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13045-021-01197-w","article-title":"Targeting CD47 for cancer immunotherapy","volume":"14","author":"Jiang","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e2304943120","DOI":"10.1073\/pnas.2304943120","article-title":"CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis","volume":"120","author":"Komori","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cell.2009.05.045","article-title":"CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells","volume":"138","author":"Majeti","year":"2009","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"872999","DOI":"10.3389\/fonc.2022.872999","article-title":"The Differential Expression of CD47 may be Related to the Pathogenesis From Myelodysplastic Syndromes to Acute Myeloid Leukemia","volume":"12","author":"Yan","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2009.05.046","article-title":"CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis","volume":"138","author":"Jaiswal","year":"2009","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"11103","DOI":"10.1073\/pnas.1305569110","article-title":"Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response","volume":"110","author":"Tseng","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1182\/blood-2019-125363","article-title":"A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and\/or Refractory (R\/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results","volume":"134","author":"Zeidan","year":"2019","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1182\/blood-2019-126271","article-title":"The First-in-Class Anti-CD47 Antibody Magrolimab (5F9) in Combination with Azacitidine Is Effective in MDS and AML Patients: Ongoing Phase 1b Results","volume":"134","author":"Sallman","year":"2019","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"S290","DOI":"10.1016\/S2152-2650(21)01694-3","article-title":"AML-196: The First-in-Class Anti-CD47 Antibody Magrolimab in Combination with Azacitidine Is Well Tolerated and Effective in AML Patients: Phase 1b Results","volume":"21","author":"Sallman","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_100","unstructured":"(2023). Gilead To Discontinue Phase 3 ENHANCE Study of Magrolimab Plus Azacitidine in Higher-Risk MDS, Gilead Sciences."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood-2020-134391","article-title":"A Phase I\/IIa Study of Lemzoparlimab, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and\/or Refractory Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS): Initial Phase I Results","volume":"136","author":"Qi","year":"2020","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"9046","DOI":"10.1182\/blood-2022-157606","article-title":"Evorpacept (ALX148), a CD47-Blocking Myeloid Checkpoint Inhibitor, in Combination with Azacitidine and Venetoclax in Patients with Acute Myeloid Leukemia (ASPEN-05): Results from Phase 1a Dose Escalation Part","volume":"140","author":"Przespolewski","year":"2022","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nri.2017.108","article-title":"The diverse functions of the PD1 inhibitory pathway","volume":"18","author":"Sharpe","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1600-065X.2009.00767.x","article-title":"PD-1 signaling in primary T cells","volume":"229","author":"Riley","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_106","first-page":"727","article-title":"PD-1\/PD-L1 pathway: Current researches in cancer","volume":"10","author":"Han","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Brodsk\u00e1, B., Otev\u0159elov\u00e1, P., \u0160\u00e1lek, C., Fuchs, O., Ga\u0161ov\u00e1, Z., and Ku\u017eelov\u00e1, K. (2019). High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112823"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40164-022-00263-4","article-title":"Targeting PD-1\/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia","volume":"11","author":"Yang","year":"2022","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1002\/cncr.31896","article-title":"The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia","volume":"125","author":"Williams","year":"2019","journal-title":"Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1158\/1078-0432.CCR-19-3003","article-title":"Characterization of Immune Dysfunction and Identification of Prognostic Immune-Related Risk Factors in Acute Myeloid Leukemia","volume":"26","author":"Tang","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Damiani, D., and Tiribelli, M. (2023). Checkpoint Inhibitors in Acute Myeloid Leukemia. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061724"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7026","DOI":"10.1200\/JCO.2017.35.15_suppl.7026","article-title":"Phase IB\/II study of nivolumab with azacytidine (AZA) in patients (pts) with relapsed AML","volume":"35","author":"Daver","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1182\/blood.V130.Suppl_1.815.815","article-title":"Phase 2 Study of Combination of Cytarabine, Idarubicin, and Nivolumab for Initial Therapy of Patients with Newly Diagnosed Acute Myeloid Leukemia","volume":"130","author":"Ravandi","year":"2017","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e480","DOI":"10.1016\/S2352-3026(19)30114-0","article-title":"Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: A single-arm, phase 2 study","volume":"6","author":"Ravandi","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7014","DOI":"10.1200\/JCO.2018.36.15_suppl.7014","article-title":"Nivolumab (Nivo) maintenance (maint) in high-risk (HR) acute myeloid leukemia (AML) patients","volume":"36","author":"Kadia","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41408-021-00453-z","article-title":"Nivolumab maintenance in high-risk acute myeloid leukemia patients: A single-arm, open-label, phase II study","volume":"11","author":"Reville","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1182\/blood-2022-157326","article-title":"Randomized Phase II Study to Assess the Role of Nivolumab As Single Agent to Eliminate Minimal Residual Disease and Maintain Remission in Acute Myelogenous Leukemia (AML) Patients after Chemotherapy (NCI9706 protocol; REMAIN Trial)","volume":"140","author":"Liu","year":"2022","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1182\/blood-2019-127345","article-title":"Multi-Center Phase 2 Study of Pembroluzimab (Pembro) and Azacitidine (AZA) in Patients with Relapsed\/Refractory Acute Myeloid Leukemia (AML) and in Newly Diagnosed (\u226565 Years) AML Patients","volume":"134","author":"Gojo","year":"2019","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e003392","DOI":"10.1136\/jitc-2021-003392","article-title":"Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia","volume":"10","author":"Goswami","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1158\/2643-3230.BCD-21-0070","article-title":"Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed\/Refractory Acute Myeloid Leukemia","volume":"2","author":"Zeidner","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jtct.2021.08.022","article-title":"Safety and Efficacy of Pembrolizumab Prior to Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia","volume":"27","author":"Tschernia","year":"2021","journal-title":"Transplant. Cell. Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1182\/bloodadvances.2023010477","article-title":"Phase 2 Study of PD-1 blockade following autologous transplantation for patients with AML ineligible for allogeneic transplant","volume":"7","author":"Solomon","year":"2023","journal-title":"Blood Adv."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1182\/bloodadvances.2021006138","article-title":"A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML","volume":"6","author":"Zeidan","year":"2022","journal-title":"Blood Adv."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/ni1271","article-title":"The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity","volume":"6","author":"Zhu","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1182\/blood-2011-11-392951","article-title":"Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity","volume":"119","author":"Ndhlovu","year":"2012","journal-title":"Blood"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e23849","DOI":"10.4161\/onci.23849","article-title":"TIM3(+)FOXP3(+) regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer","volume":"2","author":"Sakuishi","year":"2013","journal-title":"Oncoimmunology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.leukres.2014.03.018","article-title":"Elevated TIM3+ hematopoietic stem cells in untreated myelodysplastic syndrome displayed aberrant differentiation, overproliferation and decreased apoptosis","volume":"38","author":"Tao","year":"2014","journal-title":"Leuk. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.clml.2021.03.009","article-title":"Leukemic Stem Cell (CD34(+)\/CD38(-)\/TIM3(+)) Frequency in Patients with Acute Myeloid Leukemia: Clinical Implications","volume":"21","author":"Mohamed","year":"2021","journal-title":"Clin. Lymphoma. Myeloma Leuk."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Tan, J., Yu, Z., Huang, J., Chen, Y., Huang, S., Yao, D., Xu, L., Lu, Y., Chen, S., and Li, Y. (2020). Increased PD-1+Tim-3+ exhausted T cells in bone marrow may influence the clinical outcome of patients with AML. Biomark. Res., 8.","DOI":"10.1186\/s40364-020-0185-8"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e330","DOI":"10.1038\/bcj.2015.58","article-title":"PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation","volume":"5","author":"Kong","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_131","first-page":"6880","article-title":"Tim-3 is highly expressed in T cells in acute myeloid leukemia and associated with clinicopathological prognostic stratification","volume":"7","author":"Li","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3233\/CBM-181368","article-title":"Up-regulation of regulatory T cells, CD200 and TIM3 expression in cytogenetically normal acute myeloid leukemia","volume":"22","author":"Zahran","year":"2018","journal-title":"Cancer Biomark."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"57811","DOI":"10.18632\/oncotarget.11063","article-title":"Acute myeloid leukemia stem cell markers in prognosis and targeted therapy: Potential impact of BMI-1, TIM-3 and CLL-1","volume":"7","author":"Darwish","year":"2016","journal-title":"Oncotarget"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.stem.2010.11.014","article-title":"TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells","volume":"7","author":"Kikushige","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"S188","DOI":"10.1016\/S2152-2650(20)30728-X","article-title":"AML-190: Anti-TIM-3 Antibody MBG453 in Combination with Hypomethylating Agents (HMAs) in Patients with High-Risk Myelodysplastic Syndrome (HR-MDS) and Acute Myeloid Leukemia: A Phase 1 Study","volume":"20","author":"Brunner","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1182\/blood-2021-146039","article-title":"Efficacy and Safety of Sabatolimab (MBG453) in Combination with Hypomethylating Agents (HMAs) in Patients (Pts) with Very High\/High-Risk Myelodysplastic Syndrome (vHR\/HR-MDS) and Acute Myeloid Leukemia (AML): Final Analysis from a Phase Ib Study","volume":"138","author":"Brunner","year":"2021","journal-title":"Blood"},{"key":"ref_137","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":"229","author":"Nolte","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_138","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":"214","author":"Riether","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.3324\/haematol.2022.281563","article-title":"Results from a phase I\/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy","volume":"108","author":"Pabst","year":"2023","journal-title":"Haematologica"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1182\/blood-2021-150371","article-title":"Safety and Efficacy of Cusatuzumab in Combination with Venetoclax and Azacitidine (CVA) in Patients with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Not Eligible for Intensive Chemotherapy; An Open-Label, Multicenter, Phase 1b Study","volume":"138","author":"Roboz","year":"2021","journal-title":"Blood"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2017-06-741033","article-title":"CTLA-4: A moving target in immunotherapy","volume":"131","author":"Rowshanravan","year":"2018","journal-title":"Blood"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13045-020-00853-x","article-title":"Expression patterns of immune checkpoints in acute myeloid leukemia","volume":"13","author":"Chen","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/14653240500499507","article-title":"CTLA-4 blockade by a human MAb enhances the capacity of AML-derived DC to induce T-cell responses against AML cells in an autologous culture system","volume":"8","author":"Zhong","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1182\/blood-2008-07-168468","article-title":"CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation","volume":"113","author":"Bashey","year":"2009","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1182\/blood.2022017686","article-title":"Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-na\u00efve settings","volume":"141","author":"Garcia","year":"2023","journal-title":"Blood"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Kotwica-Mojzych, K., Jod\u0142owska-J\u0119drych, B., and Mojzych, M. (2021). CD200:CD200R Interactions and Their Importance in Immunoregulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041602"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/leu.2011.1","article-title":"CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia","volume":"25","author":"Coles","year":"2011","journal-title":"Leukemia"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s13277-012-0578-x","article-title":"Upregulation of CD200 is associated with Foxp3+ regulatory T cell expansion and disease progression in acute myeloid leukemia","volume":"34","author":"Memarian","year":"2013","journal-title":"Tumour Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/ejh.12915","article-title":"ABCG2 and CD200 define patients at high risk of relapse in ELN favorable subgroup of AML","volume":"99","author":"Tiribelli","year":"2017","journal-title":"Eur. J. Haematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.leukres.2017.04.001","article-title":"High CD200 expression is associated with poor prognosis in cytogenetically normal acute myeloid leukemia, even in FlT3-ITD-\/NPM1+ patients","volume":"58","author":"Tiribelli","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"743","DOI":"10.31557\/APJCP.2020.21.3.743","article-title":"Clinical Significance of CD200 and CD56 Expression in Patients with Acute Myeloid Leukemia","volume":"21","author":"Aref","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e002968","DOI":"10.1136\/jitc-2021-002968","article-title":"Overexpression of CD200 is a Stem Cell-Specific Mechanism of Immune Evasion in AML","volume":"9","author":"Herbrich","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/bjh.17125","article-title":"Use of an anti-CD200-blocking antibody improves immune responses to AML in vitro and in vivo","volume":"193","author":"Rastogi","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e001014","DOI":"10.1136\/jitc-2020-001014","article-title":"LAG-3: From molecular functions to clinical applications","volume":"8","author":"Maruhashi","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/tan.13872","article-title":"The immune checkpoints Cytotoxic T lymphocyte antigen-4 and Lymphocyte activation gene-3 expression is up-regulated in acute myeloid leukemia","volume":"96","author":"Radwan","year":"2020","journal-title":"HLA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1111\/ajco.13236","article-title":"Higher frequency of the CTLA-4(+) LAG-3(+) T-cell subset in patients with newly diagnosed acute myeloid leukemia","volume":"16","author":"Chen","year":"2020","journal-title":"Asia. Pac. J. Clin. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41375-021-01350-x","article-title":"Catch me if you can: How AML and its niche escape immunotherapy","volume":"36","author":"Tettamanti","year":"2022","journal-title":"Leukemia"}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/10\/10\/1228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:09:15Z","timestamp":1760130555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/10\/10\/1228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,20]]},"references-count":157,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["bioengineering10101228"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering10101228","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,20]]}}}