Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene transduced human T cells


  • S.A. Xue
  • L. Gao
  • D. Hart
  • R. Gillmore
  • W. Qasim
  • A. Thrasher
  • J. Apperley
  • B. Engels
  • W. Uckert
  • E. Morris
  • H.J. Stauss


  • Blood


  • Blood 106: 3062-3067


  • Cytotoxic T lymphocytes (CTLs) specific for an HLA-A2-presented peptide epitope of the Wilms tumor antigen-1 (WT1) can selectively kill immature human leukemia progenitor and stem cells in vitro. In this study we have used retroviral gene transfer to introduce a WT1-specific T-cell receptor (TCR) into T lymphocytes obtained from patients with leukemia and from healthy donors. TCR-transduced T cells kill leukemia cells in vitro and display WT1-specific cytokine production. Intravenous injection of TCR-transduced T cells into nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice harboring human leukemia cells resulted in leukemia elimination, whereas transfer of control T cells transduced with an irrelevant TCR was ineffective. The data suggest that adoptive immunotherapy with WT1-TCR gene-modified patient T cells should be considered for the treatment of leukemia.