Submitted February 2, 2009
Accepted April 5, 2009
A clinical and immunological phase II trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS
Ulrich Keilholz*, Anne Letsch, Antonia Busse, Anne Marie Asemissen, Sandra Bauer, Igor Wolfgang Blau, Wolf-Karsten Hofmann, Lutz Uharek, Eckhard Thiel, and Carmen Scheibenbogen
Department of Hematology and Oncology, Charite, CBF, Berlin, Germany
Department of Medical Immunology, Charite, CCM, Berlin, Germany
* Corresponding author; email: ulrich.keilholz{at}charite.de.
This study investigated the immunogenicity of WT1 peptide vaccination in WT1-expressing AML and MDS patients without curative treatment option. Vaccination consisted of 62.5µg GM-CSF s.c. days 1-4, and 0.2mg WT1.126-134 peptide and 1mg keyhole limpet hemocyanin (KLH) on day 3. The initial 9 patients (cohort 1) received 4 vaccinations biweekly, then monthly and the subsequent 10 patients (cohort 2) continuously biweekly vaccinations. T cell responses were measured by tetramer and cytokine flow cytometry. WT1 levels were assessed by qRT-PCR. Seventeen AML patients and 2 RAEB patients received a median of 11 vaccinations. Treatment was well tolerated. Objective responses in AML patients were 10 stable diseases (SD) including 4 SD with >50% blast reduction and 2 with hematologic improvement. Additional 4 patients had clinical benefit after initial progression including 1 complete remission and 3 SD. WT1 mRNA-levels decreased at least 3-fold from baseline in 35% of patients. In 8 of 18 patients WT1-tetramer+ T cells increased in blood and in 8 of 17 patients in bone marrow, with a median frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunological, molecular and preliminary evidence of potential clinical efficacy in AML patients warranting further investigations.
