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First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience
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First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience
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Journal Article
First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience
2022
Overview
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.To conclude, our data provide evidence of potential clinical efficacy of WT1 protein-based vaccination therapy in AML patients, warranting further investigations.
Publisher
Springer Nature B.V
Subject
