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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3062-3067.
Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-01-0146.
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IMMUNOBIOLOGY
Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene–transduced human T cells
Shao-An Xue,
Liquan Gao,
Daniel Hart,
Roopinder Gillmore,
Waseem Qasim,
Adrian Thrasher,
Jane Apperley,
Boris Engels,
Wolfgang Uckert,
Emma Morris, and
Hans Stauss
From the Department of Immunology and Molecular Pathology, University College London, Royal Free Hospital, London, United Kingdom; Department of Hematology, Imperial College, London, United Kingdom; Molecular Immunology Unit, Institute of Child Health & Great Ormond Street Hospital, London, United Kingdom; and Institute of Biology, Humboldt-University Berlin, Max-Delbrück-Center of Molecular Medicine, Robert-Rössle-Straße, Berlin, Germany.
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.
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