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Antilung Cancer Effect of WT1-specific Cytotoxic T Lymphocytes¹

First Department of Internal Medicine, Ehime University School of Medicine, Ehime 791-0295 [M. M., T. A., S. F., M. Y.]; Department of Biopathological Science, Graduate School of Medicine and Dentistry, Okayama University Graduate Schools, Okayama 700-8558 [M. M., A. H., M. T.]; Department of Clinical Laboratory Science, Osaka University Medical School, Osaka 565-0871 [A. T., Y. O., H. S.]; and Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582 [M. H.], Japan

We and other groups have recently reported that CTLs that specifically recognize a peptide derived from WT1 lyse leukemia cells in a HLA class I-restricted manner. Because WT1 is expressed in various solid tumors as well as in leukemic cells, we investigated whether WT1-specific CTLs can also inhibit the growth of lung cancer by examining their cytotoxic activity against lung cancer cell lines in vitro and their inhibitory effect on the growth of human lung cancer cells engrafted into nude mice. The WT1 transcript was detected in most of the lung cancer cell lines examined. A WT1-specific, HLA-A24-restricted CTL clone (designated TAK-1) exhibited cytotoxicity against lung cancer cell lines bearing HLA-A24 but did not lyse cells lacking this HLA. This suggests that the target antigen for TAK-1 on HLA-A24-positive lung cancer cells is the naturally processed WT1 peptide. Adoptive transfer of TAK-1 into nude mice that had been engrafted with a HLA-A24-positive lung cancer cell line resulted in inhibition of cancer cell growth and prolonged survival. These findings strongly suggest that WT1 is a universal tumor-associated antigen and that WT1-targeting immunotherapy offers a potentially effective treatment option for lung cancer as well as leukemia.

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