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First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience.
Kreutmair, Stefanie; Pfeifer, Dietmar; Waterhouse, Miguel; Takács, Ferenc; Graessel, Linda; Döhner, Konstanze; Duyster, Justus; Illert, Anna Lena; Frey, Anna-Verena; Schmitt, Michael; Lübbert, Michael.
Afiliación
  • Kreutmair S; Department of Internal Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, 79106, Freiburg, Germany.
  • Pfeifer D; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner site Freiburg, 69120, Heidelberg, Germany.
  • Waterhouse M; Department of Internal Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, 79106, Freiburg, Germany.
  • Takács F; Department of Internal Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, 79106, Freiburg, Germany.
  • Graessel L; Center for Pathology, University Medical Center, University of Freiburg, 79106, Freiburg, Germany.
  • Döhner K; 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085, Budapest, Hungary.
  • Duyster J; Department of Internal Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, 79106, Freiburg, Germany.
  • Illert AL; Department of Internal Medicine III, University Hospital, 89081, Ulm, Germany.
  • Frey AV; Department of Internal Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, 79106, Freiburg, Germany.
  • Schmitt M; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner site Freiburg, 69120, Heidelberg, Germany.
  • Lübbert M; Department of Internal Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, 79106, Freiburg, Germany.
Cancer Immunol Immunother ; 71(12): 2913-2928, 2022 Dec.
Article en En | MEDLINE | ID: mdl-35476127
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Vacunas contra el Cáncer Límite: Aged / Humans / Middle aged Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Vacunas contra el Cáncer Límite: Aged / Humans / Middle aged Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania