Antilung cancer effect of WT1-specific cytotoxic T lymphocytes.
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.
Makita
Masanori
M
First Department of Internal Medicine, Ehime University School of Medicine, Ehime 791-0295, Japan.
Hiraki
Akio
A
Azuma
Taichi
T
Tsuboi
Akihiro
A
Oka
Yoshihiro
Y
Sugiyama
Haruo
H
Fujita
Shigeru
S
Tanimoto
Mitsune
M
Harada
Mine
M
Yasukawa
Masaki
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D010455:Peptides; D012333:RNA, Messenger; D025721:WT1 Proteins