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Even with the most sophisticated chemotherapy regimens, the majority of patients with acute myeloid leukemia will eventually experience a relapse and die from their disease. New treatments are needed to prevent relapse of disease in these patients. Immunotherapy using the host immune system to combat leukemia represents an exciting and potentially efficacious addition to standard chemotherapy for AML. Immune-base treatments may be particularly effective when administered at a time when patients are in clinical remission with normal blood counts; nevertheless, these patients often have minimal residual disease which eventually results in disease relapse. Successful vaccinationbased immunotherapy targeting leukemia-specific antigens will likely require the administration of powerful immune adjutants and removal of negative immune regulatory pathways in order to achieve maximal efficacy. This review article will focus on the rationales underlying our ongoing clinical trial to test the efficacy of WT1 peptide based immunotherapy using TLR3 agonist as adjuvant in combination of the depletion of T regulatory cells with anti-CD25 antibody in patients with hematologic malignancies.