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Cancer vaccines possibly inducing robust and broad anti\u2010tumor immune responses may be a promising treatment option for HM. Few effective vaccines against blood cancers are, however, developed to date partly owing to insufficient stimulation of dendritic cells (DCs) in the body and lacking appropriate tumor antigens (Ags). Here it is found that systemic multifunctional nanovaccines consisting of nucleotide\u2010binding oligomerization domain\u2010containing protein 2 (NOD2) and Toll\u2010like receptor 9 (TLR9) agonists \u2013 muramyl dipeptide (MDP) and CpG, and tumor cell lysate (TCL) as Ags (MCA\u2010NV) induce potent and broad immunity against AML. MCA\u2010NV show complementary stimulation of DCs and prime homing to lymphoid organs following systemic administration. Of note, in orthotopic AML mouse models, intravenous infusion of different vaccine formulations elicits substantially higher anti\u2010AML efficacies than subcutaneous administration. Systemic MCA\u2010NV cure 78% of AML mice and elicit long\u2010term immune memory with 100% protection from rechallenging AML cells. Systemic MCA\u2010NV can also serve as prophylactic vaccines against the same AML. These systemic nanovaccines utilizing patient TCL as Ags and dual adjuvants to elicit strong, durable, and broad immune responses can provide a personalized immunotherapeutic strategy against AML and other HM.<\/jats:p>","DOI":"10.1002\/adma.202407189","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T17:07:12Z","timestamp":1724346432000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Systemic Multifunctional Nanovaccines for Potent Personalized Immunotherapy of Acute Myeloid Leukemia"],"prefix":"10.1002","volume":"36","author":[{"given":"Peng","family":"Zhang","sequence":"first","affiliation":[{"name":"Biomedical Polymers Laboratory College of Chemistry Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection Soochow University  Suzhou 215123 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-641X","authenticated-orcid":false,"given":"Tianhui","family":"Liu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Hematologic Diseases Jiangsu Institute of Hematology The First Affiliated Hospital of Soochow University Collaborative Innovation Center of Hematology Soochow University  Suzhou 215000 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6545-7867","authenticated-orcid":false,"given":"Yiran","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases Soochow University  Suzhou 215123 P. R. 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