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. 2002 Sep 15;100(6):2132-7.
doi: 10.1182/blood-2002-01-0163.

CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia

Carmen Scheibenbogen  1 , Anne Letsch, Eckhard Thiel, Alexander Schmittel, Volker Mailaender, Steffi Baerwolf, Dirk Nagorsen, Ulrich Keilholz
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Free article

CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia

Carmen Scheibenbogen et al. Blood. .
Free article

Abstract

Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models. We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients. T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only. T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells. In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+). These results provide for the first time evidence for spontaneous T-cell reactivity against defined antigens in AML patients. These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.

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