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

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.

• Authors: Shao-An Xue, Liquan Gao, Daniel Hart, Roopinder Gillmore, Waseem Qasim, Adrian Thrasher, Jane Apperley, Boris Engels, Wolfgang Uckert, Emma Morris, Hans Stauss
• Journal: Blood (Blood) Vol. 106 Issue 9 Pg. 3062-7 (Nov 01 2005) ISSN: 0006-4971 [Print] United States
• PMID: 16020516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Antigen, T-Cell
• WT1 Proteins

Topics

• Animals
• Cell Line
• Cell Proliferation
• Genes, T-Cell Receptor (genetics, physiology)
• Health
• Humans
• Immunotherapy (methods)
• Leukemia (genetics, immunology, metabolism, pathology)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Receptors, Antigen, T-Cell (genetics, metabolism)
• T-Lymphocytes (immunology, metabolism)
• Transgenes (genetics)
• WT1 Proteins (genetics, metabolism)