Volume 4 Supplement 1

Association for Immunotherapy of Cancer: Cancer Immunotherapy – 2nd Annual Meeting

Open Access

Vaccination with WT1 induces high frequency memory and effector T cells in peripheral blood and bone marrow associated with complete remission of recurrent AML

  • A Letsch1Email author,
  • C Scheibenbogen1,
  • AM Asemissen1,
  • V Mailänder1,
  • E Thiel1 and
  • U Keilholz1
Cancer Cell International20044(Suppl 1):S17

https://doi.org/10.1186/1475-2867-4-S1-S17

Received: 28 April 2004

Published: 1 July 2004

The transcription factor Wilms tumor protein 1 (WT1) is an interesting antigen for use in vaccination and T cell therapy in myeloid leukemias. WT1 is strongly expressed in the majority of myeloid leukemic blasts and is a key molecule for blast proliferation. A phase I/II study has been initiated in our institution in patients with acute myeloid leukemia to analyze the immunogenicity and toxicity of WT1 126–134 peptide vaccination ín combination with the adjuvants GM-CSF and keyhole limpet hemocyanin. We report here on the first 4 patients who have completed vaccination and have received a total of 15, 12, 5, and 5 vaccination cycles, respectively. While, following chemotherapy, patients 1 and 2 both had 5–10% blasts in bone marrow when vaccination was initiated, patient 3 and 4 had 90% and 70% blasts, respectively. Induction of high frequency T cell responses was detected in 3 of 4 patients with up to 0.92%, 0.43%, and 0.42% in peripheral blood and up to 0.8% in bone marrow by tetramer analysis. Detailed phenotypical analysis in patient 1 showed that WT1-specific peripheral blood T cells were almost exclusively CD45RA+CCR7-granzymeB+, and directly produced IFNγ in response to WT1 peptide, resembling cytotoxic effector T cells, while in the bone marrow both WT1-specific effector and CD45RA-CCR7- effector memory T cells were found. Patient 3 and 4 had progressive disease after 5 vaccinations. Patient 1 who had progressed during the first 4 weeks of vaccination with an increase of blasts to 30% in bone marrow was induced into complete remission after 6 vaccinations, which lasted for 12 months. Patient 2 is in continuous remission for currently 20 months. WT1 transcripts in bone marrow and peripheral blood were quantitated by PCR to monitor residual disease. In accordance with the clinical course in patients 1 and 2 we observed an approximately 100-fold, and 50-fold reduction, respectively, of WT1 transcripts following vaccination. No side effects as those typically seen with GM-CSF were noted. Taken together, these findings underline the efficacy of the vaccine, inducing high frequency WT1-specific effector and memory T cells in peripheral blood and bone marrow associated with complete remission of leukemia in the absence of hematological or renal toxicity.

Authors’ Affiliations

(1)
Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Charité, Campus Benjamin Franklin

Copyright

© Author(s); licensee BioMed Central Ltd. 2004

Advertisement