Expression of antigens associated with small cell carcinoma of the lung on hematopoietic progenitor cells.
We have previously described a panel of four monoclonal antibodies (MoAbs) reactive with antigens expressed on tumor cells from small cell carcinoma of the lung (SCCL). These IgM MoAbs are cytotoxic to SCCL cells in the presence of complement and thus have potential as reagents for the removal of SCCL cells contaminating bone marrow autografts. Therefore, we examined the cytotoxicity of these MoAbs against normal hematopoietic progenitor cells as a preliminary step toward their use in clinical trials. In this paper we report the results of treating normal bone marrow and peripheral blood mononuclear cells with the four IgM MoAbs, as well as an IgG2a MoAb that we have recently prepared against an SCCL cell line, DMS 406. Peripheral blood and bone marrow mononuclear cells were treated with the MoAbs alone or in combination, in the presence of rabbit complement, and then plated into colony-forming assays. Notably, only one MoAb, SCCL-1, had any demonstrable cytotoxicity against progenitor cells. This toxicity was limited to bone marrow burst-forming unit-erythroid and all classes of blood progenitor cells. A MoAb cocktail containing a combination of either four or five MoAbs + complement spared most marrow progenitor cells. These studies extend the base of information regarding the expression of SCCL-associated antigens on hematopoietic cells and indicate that selected MoAbs may be used safely for the removal of SCCL cells from autografts by complement-dependent lysis or other means.
Ball
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Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756.
Keefe
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Colby
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D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D018288:Carcinoma, Small Cell / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm