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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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Submitted January 19, 2005
Accepted April 20, 2005
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 J Stauss*
Department of Immunology and Molecular Pathology, University College London, Royal Free Hospital, London, United Kingdom
Molecular Immunology Unit, Institute of Child Health & Great Ormond Street Hospital, London, United Kingdom
Department of Hematology, Imperial College London, London, United Kingdom
Institute of Biology, Humboldt -University Berlin, Max-Delbruck-Center of Molecular Medicine, Berlin, Germany
* Corresponding author; email: h.stauss{at}medsch.ucl.ac.uk.
CTL specific for an HLA-A2-presented peptide epitope of the Wilms tumor antiegn-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 TCR into T lymphocytes obtained from leukemia patients 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 NOD/SCID mice harbouring human leukemia cells resulted in leukemia elimination, whilst 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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