HLA class I-restricted lysis of leukemia cells by a CD8(+) cytotoxic T-lymphocyte clone specific for WT1 peptide

The Wilms tumor (WT1) gene has been reported to be preferentially expressed in acute leukemia cells, regardless of leukemia subtype and chronic myelog enous leukemia cells in blast crisis, but not in normal cells. This finding suggests strongly that WT1 protein is a potential target of immunotherapy for human leukemia. In this study, we established a CD8(+) cytotoxic T-lymp hocyte (CTL) clone directed against a WT1-derived peptide and examined its immunologic actions on leukemia cells. A CD8(+) CTL clone, designated TAK-1 , which lysed autologous cells loaded with a WT1-derived g-mer peptide cons isting of the HLA-A24 (HLA-A*2402)-binding motifs was established by stimul ating CD8(+) T lymphocytes from a healthy individual repeatedly with WT1 pe ptide-pulsed autologous dendritic cells. TAK-1 was cytotoxic to HLA-A24-pos itive leukemia cells expressing WT1, but not to HLA-A24-positive lymphoma c ells that did not express WT1, HLA-A24-negative leukemia cells, or HLA-A24- positive normal cells. Treating leukemia cells with an antisense oligonucle otide complementary to the WT1 gene resulted in reduced TAK-l-mediated cyto toxicity, suggesting that target antigen of TAK-I on leukemia cells is the naturally processed WT1 peptide in the context of HLA-A24, TAK-I did not in hibit colony formation by normal bone marrow cells of HLA-A24-positive indi viduals. Because WT1 is overexpressed ubiquitously in various types of leuk emia cells, but not in normal cells, immunotherapy using WT1 peptide-specif ic CTL clones should be an efficacious treatment for human leukemia. (C) 20 00 by The American Society of Hematology.