Immunogenetics

, Volume 51, Issue 2, pp 99–107

Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1 ) product

Authors

  • Y. Oka
    • Department of Molecular Medicine, Osaka University Medical School, 2-2, Yamada-Oka, Suita City, Osaka 565-0871, Japan
  • O. A. Elisseeva
    • Department of Molecular Medicine, Osaka University Medical School, 2-2, Yamada-Oka, Suita City, Osaka 565-0871, Japan
  • A. Tsuboi
    • Department of Molecular Medicine, Osaka University Medical School, 2-2, Yamada-Oka, Suita City, Osaka 565-0871, Japan
  • H. Ogawa
    • Department of Molecular Medicine, Osaka University Medical School, 2-2, Yamada-Oka, Suita City, Osaka 565-0871, Japan
  • H. Tamaki
    • Department of Molecular Medicine, Osaka University Medical School, 2-2, Yamada-Oka, Suita City, Osaka 565-0871, Japan
  • H. Li
    • Department of Clinical Laboratory Science, Osaka University Medical School, 1-7, Yamada-Oka, Suita City, Osaka 565-0871, Japan e-mail: sugiyama@sahs.med.osaka-u.ac.jp Tel.: +81-6-68792593 Fax: +81-6-68792593
  • Y. Oji
    • Department of Clinical Laboratory Science, Osaka University Medical School, 1-7, Yamada-Oka, Suita City, Osaka 565-0871, Japan e-mail: sugiyama@sahs.med.osaka-u.ac.jp Tel.: +81-6-68792593 Fax: +81-6-68792593
  • E. H. Kim
    • Department of Molecular Medicine, Osaka University Medical School, 2-2, Yamada-Oka, Suita City, Osaka 565-0871, Japan
  • T. Soma
    • Department of Molecular Medicine, Osaka University Medical School, 2-2, Yamada-Oka, Suita City, Osaka 565-0871, Japan
  • M. Asada
    • Department of Clinical Laboratory Science, Osaka University Medical School, 1-7, Yamada-Oka, Suita City, Osaka 565-0871, Japan e-mail: sugiyama@sahs.med.osaka-u.ac.jp Tel.: +81-6-68792593 Fax: +81-6-68792593
  • K. Ueda
    • Department of Clinical Laboratory Science, Osaka University Medical School, 1-7, Yamada-Oka, Suita City, Osaka 565-0871, Japan e-mail: sugiyama@sahs.med.osaka-u.ac.jp Tel.: +81-6-68792593 Fax: +81-6-68792593
  • E. Maruya
    • Department of Research, Kyoto Red Cross Center, Kyoto, Japan
  • H. Saji
    • Department of Research, Kyoto Red Cross Center, Kyoto, Japan
  • T. Kishimoto
    • Osaka University, 1-1, Yamada-Oka, Suita City, Osaka, Japan
  • K. Udaka
    • PREST, JST and Department of Biophysics, Kyoto University, Sakyo, Kyoto, Japan
  • H. Sugiyama
    • Department of Clinical Laboratory Science, Osaka University Medical School, 1-7, Yamada-Oka, Suita City, Osaka 565-0871, Japan e-mail: sugiyama@sahs.med.osaka-u.ac.jp Tel.: +81-6-68792593 Fax: +81-6-68792593
ORIGINAL PAPER

DOI: 10.1007/s002510050018

Cite this article as:
Oka, Y., Elisseeva, O., Tsuboi, A. et al. Immunogenetics (2000) 51: 99. doi:10.1007/s002510050018

Abstract

 The product of the Wilms' tumor gene WT1 is a transcription factor overexpressed not only in leukemic blast cells of almost all patients with acute myeloid leukemia, acute lymphoid leukemia, and chronic myeloid leukemia, but also in various types of solid tumor cells. Thus, it is suggested that the WT1 gene plays an important role in both leukemogenesis and tumorigenesis. Here we tested the potential of WT1 to serve as a target for immunotherapy against leukemia and solid tumors. Four 9-mer WT1 peptides that contain HLA-A2.1-binding anchor motifs were synthesized. Two of them, Db126 and WH187, were determined to bind to HLA-A2.1 molecules in a binding assay using transporter associated with antigen processing-deficient T2 cells. Peripheral blood mononuclear cells from an HLA-A2.1-positive healthy donor were repeatedly sensitized in vitro with T2 cells pulsed with each of these two WT1 peptides, and CD8+ cytotoxic T lymphocytes (CTLs) that specifically lyse WT1 peptide-pulsed T2 cells in an HLA-A2.1-restricted fashion were induced. The CTLs also exerted specific lysis against WT1-expressing, HLA-A2.1-positive leukemia cells, but not against WT1-expressing, HLA-A2.1-negative leukemia cells, or WT1-nonexpressing, HLA-A2.1-positive B-lymphoblastoid cells. These data provide the first evidence of human CTL responses specific for the WT1 peptides, and provide a rationale for developing WT1 peptide-based adoptive T-cell therapy and vaccination against leukemia and solid tumors.

Key words Wilms' tumor geneWT1Cytotoxic T lymphocytesTumor-specific antigenImmunotherapy

Copyright information

© Springer-Verlag Berlin Heidelberg 2000