{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:43:00Z","timestamp":1790764980309,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian Ministry of Health\u2014Current research IRCCS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immunotherapy is changing the therapeutic landscape of many hematologic diseases, with immune checkpoint inhibitors, bispecific antibodies, and CAR-T therapies being its greatest expression. Unfortunately, immunotherapy in acute myeloid leukemia (AML) has given less brilliant results up to now, and the only approved drug is the antiCD33 antibody-drug conjugate gemtuzumab ozogamicin. A promising field of research in AML therapy relies on anti-leukemic vaccination to induce remission or prevent disease relapse. In this review, we analyze recent evidence on AML vaccines and their biological mechanisms. The principal proteins that have been exploited for vaccination strategies and have reached clinical experimental phases are Wilm\u2019s tumor 1, proteinase 3, and RHAMM. the majority of data deals with WT1-base vaccines, given also the high expression and mutation rates of WT1 in AML cells. Stimulators of immune responses such as TLR7 agonist and interleukin-2 have also proven anti-leukemic activity both in vivo and in vitro. Lastly, cellular vaccines mainly based on autologous or allogeneic off-the-shelf dendritic cell-based vaccines showed positive results in terms of T-cell response and safety, also in elderly patients. Compared to other immunotherapeutic strategies, anti-AML vaccines have the advantage of being a less toxic and a more manageable approach, applicable also to elderly patients with poorer performance status, and may be used in combination with currently available therapies. As for the best scenario in which to use vaccination, whether in a therapeutic, prophylactic, or preemptive setting, further studies are needed, but available evidence points to poorer results in the presence of active or high-burden disease. Given the poor prognosis of relapsed\/refractory or high-risk AML, further research is urgently needed to better understand the biological pathways that sustain its pathogenesis. In this setting, research on novel frontiers of immunotherapy-based agents, among which vaccines represent important actors, is warranted to develop new and efficacious strategies to obtain long-term disease control by immune patrolling.<\/jats:p>","DOI":"10.3390\/cancers14122994","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T11:45:44Z","timestamp":1655466344000},"page":"2994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Vaccination Therapy for Acute Myeloid Leukemia: Where Do We Stand?"],"prefix":"10.3390","volume":"14","author":[{"given":"Kordelia","family":"Barbullushi","sequence":"first","affiliation":[{"name":"Hematology & BMT Unit, Fondazione IRCCS Ca\u2019 Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy"},{"name":"Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Rampi","sequence":"additional","affiliation":[{"name":"Hematology & BMT Unit, Fondazione IRCCS Ca\u2019 Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy"},{"name":"Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Serpenti","sequence":"additional","affiliation":[{"name":"Hematology & BMT Unit, Fondazione IRCCS Ca\u2019 Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy"},{"name":"Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7958-4966","authenticated-orcid":false,"given":"Mariarita","family":"Scium\u00e8","sequence":"additional","affiliation":[{"name":"Hematology & BMT Unit, Fondazione IRCCS Ca\u2019 Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Fabris","sequence":"additional","affiliation":[{"name":"Hematology & BMT Unit, Fondazione IRCCS Ca\u2019 Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"De Roberto","sequence":"additional","affiliation":[{"name":"Hematology & BMT Unit, Fondazione IRCCS Ca\u2019 Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Stefano","family":"Fracchiolla","sequence":"additional","affiliation":[{"name":"Hematology & BMT Unit, Fondazione IRCCS Ca\u2019 Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","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"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia","volume":"383","author":"Dinardo","year":"2020","journal-title":"N. 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