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.
Xue
Shao-An
SA
Department of Immunology and Molecular Pathology, University College London, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF, United Kingdom.
Gao
Liquan
L
Hart
Daniel
D
Gillmore
Roopinder
R
Qasim
Waseem
W
Thrasher
Adrian
A
Apperley
Jane
J
Engels
Boris
B
Uckert
Wolfgang
W
Morris
Emma
E
Stauss
Hans
H
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019672:Genes, T-Cell Receptor / Q000235:genetics* / Q000502:physiology; D006262:Health; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007938:Leukemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D025721:WT1 Proteins