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

Official URL:https://doi.org/10.1182/blood-2005-01-0146
PubMed:View item in PubMed
Creators Name:Xue, S.A. and Gao, L. and Hart, D. and Gillmore, R. and Qasim, W. and Thrasher, A. and Apperley, J. and Engels, B. and Uckert, W. and Morris, E. and Stauss, H.J.
Journal Title:Blood
Journal Abbreviation:Blood
Volume:106
Page Range:3062-3067
Date:14 July 2005
Keywords:Antigen and T-Cell Receptors, Cell Line, Cell Proliferation, Health, Immunotherapy, Leukemia, T-Cell Receptor Genes, T-Lymphocytes, Transgenes, WT1 Proteins, Animals, Mice
Abstract: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.
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Item Type:Article

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