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Laboratory of Immunology, Department of Radiobiology, Radiation Effects Research Foundation [N. K., S. K., M. V., M. A.], and Second Department of Internal Medicine, Hiroshima University School of Medicine [M. T., T. O., M. Y.], Hiroshima, Japan
In the presence of a characterized monoclonal antibody recognizing a soluble molecule, additional monoclonal antibodies reactive with unknown antigenic determinants on the molecule can be easily selected by reversed indirect enzyme-linked immunosorbent assay. A novel murine monoclonal antibody, LISA 101, was selected by reversed indirect enzyme-linked immunosorbent assay against soluble antigens, which exist in sera and in pleural effusions derived from lung adenocarcinoma patients and which bear determinants recognized by the previously characterized murine monoclonal antibody KL-6. Antigenic determinants recognized by the LISA 101 antibody appear to be sialylated carbohydrate in nature and different from those recognized by previously reported monoclonal antibodies against sialylated carbohydrates, such as NS 19-9, FH-6, and KL-6, suggested by competitive inhibition assay and immunostaining of tissues. A circulating antigen, LISA 16, was detected by a bimonoclonal bideterminant assay using immobilized LISA 101 antibody and enzymelabeled KL-6 antibody. It was found that serum LISA 16 levels were elevated in 63% (25 of 40) of patients with lung adenocarcinoma and in 92% (11 of 12) of patients with pancreatic carcinoma, but only in 6.5% (2 of 31) of patients with benign lung diseases and in 7.1% (1 of 14) of patients with pancreatitis.
The present observations indicate that the LISA 16 antigen may serve as a new tumor marker for adenocarcinomas of the lung and the pancreas. Additionally, the reversed indirect enzyme-linked immunosorbent assay may be a widely applicable method for selecting new monoclonal antibodies against as yet unknown antigenic determinants on soluble molecules.
1 Supported by a grant of the Anti-Cancer Strategy Research Program from the Ministry of Health and Welfare, Japan. The Radiation Effects Research Foundation (formerly the Atomic Bomb Casualty Commission) was established in April 1975 as a private nonprofit Japanese foundation, supported equally by the Government of Japan with funding from the Ministry of Health and Welfare and the Government of the United States with funding from the Department of Energy through the National Academy of Sciences.
2 To whom requests for reprints should be addressed, at Department of Radiobiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732, Japan.
Received 9/ 6/88. Revised 3/ 8/89. Accepted 3/14/89.
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