Blood 106: 3062-3067 (2005-07-14)

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

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

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.

Keywords: Animals, WT1 Proteins, Transgenes, T-Lymphocytes, T-Cell Receptor Genes, Leukemia, Immunotherapy, Health, Cell Proliferation, Cell Line, Antigen and T-Cell Receptors, Mice

Type: Article

PubMed: 16020516
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