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Cytotoxic Murine Monoclonal Antibody LAM8 with Specificity for Human Small Cell Carcinoma of the Lung

Division of Oncology, Department of Medicine, University Hospital of Zürich, Switzerland [R. A. S., R. W.]; Division of Medicine [M. M., J. A. S., S. D. B.], and Division of Immunology [K. S.], Dana-Farber Cancer Institute and Harvard Medical School; and Department of Pathology, New England Deaconess Hospital, [C. J. O.] Boston, Massachusetts 02115

The reactivity of the murine immunoglobulin monoclonal antibody LAM8 directed against a membrane antigen of human small cell carcinoma (SCC) of the lung was investigated on human cell lines and tissues. Indirect immunofluorescence staining, radioimmunoassays, and cytotoxicity assays showed LAM8 antibody to selectively react with SCC but not with non-SCC lung cancer cell lines and extrapulmonary tumor cell lines. Unlike other SCC antibodies, including those we have previously described, highly preferential reactivity with SCC tissues was also demonstrated by immunoperoxidase staining of deparaffinized formalin-fixed tissue sections. Membrane and cytoplasmic staining was seen in of 9 of 12 SCC tissues. No significant staining was seen in non-SCC lung cancer and a wide range of other tumors, including mesothelioma and bronchial carcinoids. Significant LAM8 reactivity was also absent in normal tissues of all major organs. Few tumors and epithelial tissues, including bronchial epithelium had rare LAM8 positive cells which were always less than 2% of the entire cell population. In vitro treatment with antibody and human complement was highly cytotoxic to SCC cells, but had no effect on bone marrow progenitor cells. Immunoblotting of membrane extracts separated on sodium dodecyl sulfate-polyacrylamide gels showed the LAM8 antigen to have a band of an approximate molecular weight of 135,000 and a cluster of bands with approximate molecular weights of 90,000. This reactivity was lost after incubation of the extracts with periodate. LAM8 antibody shows a highly preferential reactivity with SCC cell lines and formalin-fixed paraffin-embedded SCC tissues and is selectively cytotoxic to cells expressing LAM8 antigen.

¹ Supported in part by fellowship DRG-029 of the Damon Runyon-Walter Winchell Cancer Fund and the Swiss Cancer League (FOR.282.LR and FOR.302.85). To whom requests for reprints should be addressed, at Division of Oncology, University Hospital, CH-8091 Zurich, Switzerland.

² Supported in part by National Cancer Institute Grants CA 36498 and CA 33847.

Received 7/30/85. Revised 10/30/85. Accepted 12/30/85.