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Abstract: Wilms' tumor 1 (WT1) protein is highly immunogenic and overexpressed in acute myeloid leukemia (AML), consequently ranked as a promising target for novel immunotherapeutic strategies. Here we report our experience of a phase I/II clinical trial (NCT01051063) of a vaccination strategy based on WT1 recombinant protein (WT1-A10) together with vaccine adjuvant AS01B in five elderly AML patients (median age 69 years, range 63-75) receiving a total of 62 vaccinations (median 18, range 3-20) after standard chemotherapy. Clinical benefit was observed in three patients: one patient achieved measurable residual disease clearance during WT1 vaccination therapy, another patient maintained long-term molecular remission over 59 months after the first vaccination cycle. Interestingly, in one case, we observed a complete clonal switch at AML relapse with loss of WT1 expression, proposing suppression of the original AML clone by WT1-based vaccination therapy. Detected humoral and cellular CD4+ T cell immune responses point to efficient immune stimulation post-vaccination, complementing hints for induced conventional T cell infiltration into the bone marrow and a shift from senescent/exhausted to a more activated T cell profile. Overall, the vaccinations with WT1 recombinant protein had an acceptable safety profile and were thus well tolerated.<br><br>To conclude, our data provide evidence of potential clinical efficacy of WT1 protein-based vaccination therapy in AML patients, warranting further investigations