Cytotoxic murine monoclonal antibody LAM8 with specificity for human small cell carcinoma of the lung

24 breast, gastric, and colonic adenocarcinomas and some tumors of neuroectodermal origin. Group 2 antibodies, which are both of IgG3 subclass imnxnoprecipitate a nonglycosylated MSr) 24,000 polypeptide. Group 3 antibodies (PF3/A, an IgGl; PF3/B, and IgGM; and PF3/C, an IgG2a) react additionally with certain other tumors, as well as with normal adult and fetal epidermis. Group 4 antibodies (PF4/A, an IgG2a; and PF4/B, an IgGl) are less specific than those of the preceding groups, as they react with some normal tissues, including pancreatic islets and pneumocytes, as well as with a variety of adenocarcinomas and tumors of neuroectodermal origin. PF4/A and PF4/B immunoprecipitate (M(r) I00,000 and 95,000 glycoproteins, respectively. Cytotoxic Murine Monoclonal Antibody LAM8 With Specificity for Human Small Cell Carcinoma of the Lung. Stahel, R.A., O'Hara, C.J., Mabry, M. et al. Division of Oncology, Department of Medicine, University Hospital of Zurich, CH8091 Zurich, Switzerland. Cancer Res. 46: 2077-2084, 1986. The reactivity of the murine immunoglobulin monoclonal antibody LAM8 directed against a membrane antigen of ~ m ~ n small cell carcinoma (SCC) of the lung was investigated on human cell lines and tissues. Indirect immmofluorescence 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 ~,nnn 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 formalinfixed paraffin-embedded SCC tissues and is selectively cytotoxic to cells expressing LAM8 antigen. Anti-Neurofilament Antibodies in the Sera of Patients with Small Cell Carcinoma of the Lung and With Visual Paraneop lastic Syndrome. Kornguth, S.E., Kalinke, T., Grunwald, G.B. et al. Department of Neurology, University of Wisconsin, Madison, WI, U.S.A. Cancer Res. 46: 2588-2595, 1986. The sera of patients with small cell caricnoma of the lung (SCCL) and an associated visual paraneoplastic syndrome (VPNS) have higher titer ~ o g l o b u l i n s that react with retinal ganglion cells and with cloned lines of the SCCL. The immunoglobulins in the sera of two patients with SCCL and VPNS reacted with at least one common antigen shared by neural cells and cloned lines of the SCCL. The molecular weights of the predominant neural and tumor antigens were 205,000, 145,000, 65,000, and 20,000-24,000 as determined by Western blots. Three of the antigens from neural tissue copurify and comigrate electrophoretically with neurofilament proteins. Polyclonal antibodies prepared against authentic neurofilament proteins react with antigens having molecular weights identical to those of proteins t_hat react with immunoglobulins form the SCCL-VPNS patients. Polyclonal antibodies that were prepared against isolated retinal ganglion cells and that were shown previously to cause the inmn/noablation of the ganglion cells in vivo reacted most intensely with the M(r) 205,000 antigen and weakly with the M(r) 145,000 and M(r) 70,000 antigens. Treatment of the Western blots with alkaline phosphatase from Escherichia coli did not affect the immunoreactivity between the immunoglobulins and the purified neurofilament proteins. It is proposed t_hat the immunoglobulins in the sera of patients with SCCL-VPNS may be involved etiologically in the development of the VPNS.