{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:56:20Z","timestamp":1783065380437,"version":"3.54.6"},"reference-count":95,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AGING Project\u2014Department of Excellence\u2014DIMET, Universit\u00e0 del Piemonte Orientale, Novara, Italy"},{"name":"Digital Morphology Program, Novara-AIL Onlus, Novara, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML\/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML\/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML\/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. These novel mAbs are currently under investigation for use as monotherapy or in combination with hypomethylating agents, BCL2 inhibitors, and chemotherapy in various clinical trials at different phases of development. Here, we review the main molecular targets and modes of action of novel mAb-based immunotherapies, which can represent the future of AML and higher risk MDS treatment.<\/jats:p>","DOI":"10.3390\/ijms23147542","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T22:11:47Z","timestamp":1657231907000},"page":"7542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes"],"prefix":"10.3390","volume":"23","author":[{"given":"Marco","family":"Gallazzi","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maghalie Anais Marie","family":"Ucciero","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-4207","authenticated-orcid":false,"given":"Danilo Giuseppe","family":"Faraci","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurraouf Mokhtar","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael","family":"Al Essa","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-0151","authenticated-orcid":false,"given":"Gianluca","family":"Gaidano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0389-3268","authenticated-orcid":false,"given":"Samir","family":"Mouhssine","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-0574","authenticated-orcid":false,"given":"Elena","family":"Cris\u00e0","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1182\/blood-2013-08-518886","article-title":"Clinical and biological implications of driver mutations in myelodysplastic syndromes","volume":"122","author":"Papaemmanuil","year":"2013","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/leu.2013.336","article-title":"Landscape of genetic lesions in 944 patients with myelodysplastic syndromes","volume":"28","author":"Haferlach","year":"2014","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1182\/blood-2012-03-420489","article-title":"Revised international prognostic scoring system for myelodysplastic syndromes","volume":"120","author":"Greenberg","year":"2012","journal-title":"Blood"},{"key":"ref_5","first-page":"424","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.annonc.2020.02.018","article-title":"Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Heuser","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1002\/cncr.33477","article-title":"Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach","volume":"127","author":"Kantarjian","year":"2021","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/cncr.33458","article-title":"De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017","volume":"127","author":"Sasaki","year":"2021","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/PPO.0000000000000577","article-title":"Monoclonal Antibodies in Acute Myeloid Leukemia-Are We There Yet?","volume":"28","author":"Abaza","year":"2022","journal-title":"Cancer J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kapoor, S., Champion, G., Basu, A., Mariampillai, A., and Olnes, M.J. (2021). Immune Therapies for Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cancers, 13.","DOI":"10.3390\/cancers13195026"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1200\/JCO.19.01823","article-title":"Integrating the \u201cImmunome\u201d in the Stratification of Myelodysplastic Syndromes and Future Clinical Trial Design","volume":"38","author":"Winter","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1182\/blood-2005-05-1884","article-title":"Interferon-gamma-induced gene expression in CD34 cells: Identification of pathologic cytokine-specific signature profiles","volume":"107","author":"Zeng","year":"2006","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.cell.2018.07.017","article-title":"Innate Lymphoid Cells: 10 Years on","volume":"174","author":"Vivier","year":"2018","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lordo, M.R., Scoville, S.D., Goel, A., Yu, J., Freud, A.G., Caligiuri, M.A., and Mundy-Bosse, B.L. (2021). Unraveling the Role of Innate Lymphoid Cells in AcuteMyeloid Leukemia. Cancers, 13.","DOI":"10.3390\/cancers13020320"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sendker, S., Reinhardt, D., and Niktoreh, N. (2021). Redirecting the Immune Microenvironment in Acute Myeloid Leukemia. Cancers, 13.","DOI":"10.3390\/cancers13061423"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.2217\/imt-2019-0043","article-title":"Reinforcing the primary immunotherapy modulators against acute leukemia; monoclonal antibodies in AML","volume":"11","author":"Mahalleh","year":"2019","journal-title":"Immunotherapy"},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1111\/trf.15397","article-title":"The effects of monoclonal anti-CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia","volume":"59","author":"Brierley","year":"2019","journal-title":"Transfusion"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1056\/NEJMoa1601202","article-title":"Ipilimumab for Patients with Relapse after Allogeneic Transplantation","volume":"375","author":"Davids","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1158\/2159-8290.CD-18-0774","article-title":"Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed\/Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study","volume":"9","author":"Daver","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1182\/blood-2020-142824","article-title":"Azacitidine (AZA) with Nivolumab (Nivo), and AZA with Nivo + Ipilimumab (Ipi) in Relapsed\/Refractory (R\/R) Acute Myeloid Leukemia: Clinical and Immune Biomarkers of Response","volume":"136","author":"Daver","year":"2020","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood-2020-136855","article-title":"Efficacy and Safety of Sabatolimab (MBG453) in Combination with Hypomethylating Agents (HMAs) in Patients with Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS): Updated Results from a Phase 1b Study","volume":"136","author":"Brunner","year":"2020","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1182\/blood-2018-03-841171","article-title":"A phase 1 trial of vadastuximab talirine combined with hypomethylating agents in patients with CD33-positive AML","volume":"132","author":"Fathi","year":"2018","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"TPS7066","DOI":"10.1200\/JCO.2017.35.15_suppl.TPS7066","article-title":"CASCADE: A phase 3, randomized, double-blind study of vadastuximab talirine (33A) versus placebo in combination with azacitidine or decitabine in the treatment of older patients with newly diagnosed acute myeloid leukemia (AML)","volume":"35","author":"Wang","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1016\/j.jmir.2019.05.008","article-title":"Targeted Alpha-Particle Therapy for Hematologic Malignancies","volume":"50","author":"Jurcic","year":"2019","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_27","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_28","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_29","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1182\/blood-2018-99-119786","article-title":"Complete Responses in Relapsed\/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of XmAb14045, a CD123 x CD3 T Cell-Engaging Bispecific Antibody: Initial Results of a Phase 1 Study","volume":"132","author":"Ravandi","year":"2018","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1182\/blood-2018-99-112955","article-title":"A Phase I, First-in-Human Study Evaluating the Safety and Preliminary Antileukemia Activity of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, in Patients with Relapsed\/Refractory Acute Myeloid Leukemia and Other CD123-Positive Hematologic Malignancies","volume":"132","author":"Daver","year":"2018","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e579","DOI":"10.1016\/j.clml.2021.02.008","article-title":"Combination of Tagraxofusp and Azacitidine Is an Effective Option for Relapsed Blastic Plasmacytoid Dendritic Cell Neoplasm After Allogeneic Hematopoietic Stem-Cell Transplantation","volume":"21","author":"Wang","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"5444","DOI":"10.1182\/blood-2009-03-213298","article-title":"Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome","volume":"114","author":"Pagel","year":"2009","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.3324\/haematol.2019.229492","article-title":"Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed\/refractory leukemia or myelodysplasia","volume":"105","author":"Vo","year":"2020","journal-title":"Haematologica"},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"7507","DOI":"10.1200\/JCO.2020.38.15_suppl.7507","article-title":"Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results","volume":"38","author":"Sallman","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1182\/blood-2021-146547","article-title":"Evorpacept (ALX148), a CD47-Blocking Myeloid Checkpoint Inhibitor, in Combination with Azacitidine: A Phase 1\/2 Study in Patients with Myelodysplastic Syndrome (ASPEN-02)","volume":"138","author":"Erba","year":"2021","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood-2020-142003","article-title":"A Phase II Study of Double Immune Checkpoint Inhibitor Blockade with Nivolumab and Ipilimumab with or without Azacitidine in Patients with Myelodysplastic Syndrome (MDS)","volume":"136","author":"Morita","year":"2020","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/bjh.17689","article-title":"Phase II study of azacitidine with pembrolizumab in patients with intermediate-1 or higher-risk myelodysplastic syndrome","volume":"195","author":"Chien","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1182\/blood.V128.22.227.227","article-title":"A Clinical Study of OPN-305, a Toll-like Receptor 2 (TLR-2) Antibody, in Patients with Lower Risk Myelodysplastic Syndromes (MDS) That Have Received Prior Hypomethylating Agent (HMA) Therapy","volume":"128","author":"Yang","year":"2016","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1182\/blood-2018-99-119805","article-title":"A Clinical Study of Tomaralimab (OPN-305), a Toll-like Receptor 2 (TLR-2) Antibody, in Heavily Pre-Treated Transfusion Dependent Patients with Lower Risk Myelodysplastic Syndromes (MDS) That Have Received and Failed on Prior Hypomethylating Agent (HMA) Therapy","volume":"132","author":"Jabbour","year":"2018","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood-2020-136398","article-title":"GTB-3550 TriKE\u2122 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":"Warlick","year":"2020","journal-title":"Blood"},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/2211-5463.13084","article-title":"Preclinical efficacy and toxicity studies of a highly specific chimeric anti-CD47 antibody","volume":"11","author":"Xu","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/eji.201646875","article-title":"Immune checkpoints and their inhibition in cancer and infectious diseases","volume":"47","author":"Dyck","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101247","DOI":"10.1016\/j.beha.2021.101247","article-title":"Immune checkpoint inhibitors in acute myeloid leukemia","volume":"34","author":"Daver","year":"2021","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/leu.2013.355","article-title":"Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents","volume":"28","author":"Yang","year":"2014","journal-title":"Leukemia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1074-7613(00)80123-5","article-title":"CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism","volume":"11","author":"Shrikant","year":"1999","journal-title":"Immunity"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/17474086.2018.1459184","article-title":"Checkpoint inhibitors and acute myelogenous leukemia: Promises and challenges","volume":"11","author":"Alfayez","year":"2018","journal-title":"Expert Rev. Hematol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ejca.2015.11.016","article-title":"Immune-related adverse events with immune checkpoint blockade: A comprehensive review","volume":"54","author":"Michot","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<90::AID-IMMU90>3.0.CO;2-5","article-title":"Regulation of CD80\/B7-1 and CD86\/B7-2 molecule expression in human primary acute myeloid leukemia and their role in allogenic immune recognition","volume":"28","author":"Costello","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 is a novel direct target of HIF-1\u03b1, and its blockade under hypoxia enhanced MDSC-mediated T cell activation","volume":"211","author":"Noman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1600-065X.2010.00923.x","article-title":"The PD-1 pathway in tolerance and autoimmunity","volume":"236","author":"Francisco","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3389\/fphar.2019.00609","article-title":"A Review of Efficacy and Safety of Checkpoint Inhibitor for the Treatment of Acute Myeloid Leukemia","volume":"10","author":"Liao","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/imr.12520","article-title":"Tim-3 and its role in regulating anti-tumor immunity","volume":"276","author":"Das","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"618710","DOI":"10.3389\/fimmu.2021.618710","article-title":"One Stone, Two Birds: The Roles of Tim-3 in Acute Myeloid Leukemia","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/14737140.2021.1865814","article-title":"TIM-3 pathway dysregulation and targeting in cancer","volume":"21","author":"Zeidan","year":"2021","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41577-019-0224-6","article-title":"TIM3 comes of age as an inhibitory receptor","volume":"20","author":"Wolf","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.exphem.2020.07.001","article-title":"TLR2\/6 signaling promotes the expansion of premalignant hematopoietic stem and progenitor cells in the NUP98-HOXD13 mouse model of MDS","volume":"88","author":"Monlish","year":"2020","journal-title":"Exp. Hematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1038\/leu.2013.180","article-title":"Toll-like receptor alterations in myelodysplastic syndrome","volume":"27","author":"Wei","year":"2013","journal-title":"Leukemia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1182\/blood-2015-01-621631","article-title":"IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells","volume":"125","author":"Schinke","year":"2015","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/clpt.2013.150","article-title":"Randomized, double-blind, placebo-controlled, dose-escalating phase I, healthy subjects study of intravenous OPN-305, a humanized anti-TLR2 antibody","volume":"94","author":"Reilly","year":"2013","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3324\/haematol.2018.188888","article-title":"Gemtuzumab ozogamicin for de novo acute myeloid leukemia: Final efficacy and safety updates from the open-label, phase III ALFA-0701 trial","volume":"104","author":"Lambert","year":"2019","journal-title":"Haematologica"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"101224","DOI":"10.1016\/j.beha.2020.101224","article-title":"CD33 directed bispecific antibodies in acute myeloid leukemia","volume":"33","author":"Clark","year":"2020","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Testa, U., Pelosi, E., and Castelli, G. (2019). CD123 as a Therapeutic Target in the Treatment of Hematological Malignancies. Cancers, 11.","DOI":"10.3390\/cancers11091358"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cytogfr.2013.03.002","article-title":"Signalling by the \u03b2c family of cytokines","volume":"24","author":"Hercus","year":"2013","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Allen, C., Zeidan, A.M., and Bewersdorf, J.P. (2021). BiTEs, DARTS, BiKEs and TriKEs-Are Antibody Based Therapies Changing the Future Treatment of AML?. Life, 11.","DOI":"10.3390\/life11060465"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.imlet.2018.01.009","article-title":"CD45 in human physiology and clinical medicine","volume":"196","author":"Schraven","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","unstructured":"Liu, J., Wang, L., Zhao, F., Tseng, S., Narayanan, C., Shura, L., Willingham, S., Howard, M., Prohaska, S., and Volkmer, J. (2015). Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137345"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.coi.2012.01.010","article-title":"The CD47-SIRP\u03b1 pathway in cancer immune evasion and potential therapeutic implications","volume":"24","author":"Chao","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_74","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_75","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.blre.2018.12.001","article-title":"Immunotherapy in acute myeloid leukemia and myelodysplastic syndromes: The dawn of a new era?","volume":"34","author":"Liu","year":"2019","journal-title":"Blood Rev."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kauder, S.E., Kuo, T.C., Harrabi, O., Chen, A., Sangalang, E., Doyle, L., Rocha, S.S., Bollini, S., Han, B., and Sim, J. (2018). ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201832"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1158\/1078-0432.CCR-07-4079","article-title":"Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies","volume":"14","author":"Berger","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_78","first-page":"1490","article-title":"Approval summary: Gemtuzumab ozogamicin in relapsed acute myeloid leukemia","volume":"7","author":"Bross","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1080\/17512433.2018.1478725","article-title":"Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia","volume":"11","author":"Baron","year":"2018","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_80","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_81","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.2217\/fon-2020-1287","article-title":"Comparing cure rates for gemtuzumab ozogamicin plus standard chemotherapy vs standard chemotherapy alone in acute myeloid leukemia patients","volume":"17","author":"Muresan","year":"2021","journal-title":"Future Oncol."},{"key":"ref_82","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_83","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_84","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1182\/blood-2014-04-566737","article-title":"Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients","volume":"124","author":"Frankel","year":"2014","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7068","DOI":"10.1200\/jco.2007.25.18_suppl.7068","article-title":"Induction of remission in patients with acute myeloid leukemia without prolonged myelosuppression using diphtheria toxin-interleukin 3 fusion protein","volume":"25","author":"Frankel","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"TPS7565","DOI":"10.1200\/JCO.2020.38.15_suppl.TPS7565","article-title":"CULMINATE: A phase II study of cusatuzumab + azacitidine in patients with newly diagnosed AML, ineligible for intensive chemotherapy","volume":"38","author":"Trudel","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1158\/1078-0432.CCR-17-3763","article-title":"A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure","volume":"24","author":"Zeidan","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1182\/blood.2020006158","article-title":"TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype","volume":"136","author":"Sallman","year":"2020","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4669","DOI":"10.1182\/blood-2021-145626","article-title":"Sabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program","volume":"138","author":"Zeidan","year":"2021","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1016\/j.ymthe.2022.02.005","article-title":"Immunodepletion of MDSC by AMV564, a novel bivalent, bispecific CD33\/CD3 T cell engager, ex vivo in MDS and melanoma","volume":"30","author":"Cheng","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/s41375-019-0645-z","article-title":"Single agent talacotuzumab demonstrates limited efficacy but considerable toxicity in elderly high-risk MDS or AML patients failing hypomethylating agents","volume":"34","author":"Kubasch","year":"2020","journal-title":"Leukemia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1182\/blood-2021-152463","article-title":"AFM28, a Novel Bispecific Innate Cell Engager (ICE\u00ae), Designed to Selectively Re-Direct NK Cell Lysis to CD123+ Leukemic Cells in Acute Myeloid Leukemia and Myelodysplastic Syndrome","volume":"138","author":"Pahl","year":"2021","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"521","DOI":"10.2147\/IJN.S233395","article-title":"Daunorubicin-Loaded CdTe QDs Conjugated with Anti-CD123 mAbs: A Novel Delivery System for Myelodysplastic Syndromes Treatment","volume":"15","author":"Guo","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_94","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_95","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s13045-018-0675-4","article-title":"FLT3 inhibitors in acute myeloid leukemia","volume":"11","author":"Wu","year":"2018","journal-title":"J. Hematol. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7542\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:44:08Z","timestamp":1760139848000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/14\/7542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,7]]},"references-count":95,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23147542"],"URL":"https:\/\/doi.org\/10.3390\/ijms23147542","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,7]]}}}