Monoclonal anti-human tumor antibodies of six isotypes in cytotoxic reactions with human and murine effector cells |
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| Authors: | D Herlyn M Herlyn Z Steplewski H Koprowski |
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| Affiliation: | 1. Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa, Japan;2. Department of Environmental Health, University of Occupational and Environmental Health, Japan;3. Department of Molecular Biology, Hamamatsu University School of Medicine, Japan;4. Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Japan;5. Department of Social Medicine, Saga University School of Medicine, Japan;6. Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Japan;1. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA;2. Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, La Jolla, CA, USA;1. Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand;2. Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand;3. Department of Food Science, University of Otago, PO Box 56, Dunedin, New Zealand;4. AgResearch Ltd Grasslands, Palmerston North, New Zealand |
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| Abstract: | Eighty-seven murine monoclonal antibodies (MAb) produced against human tumors of various origins and representing six different immunoglobulin classes were tested for antitumor reactivity in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays. Mouse splenocytes, thioglycolate-elicited mouse peritoneal macrophages, freshly obtained nonadherent human peripheral blood lymphocytes, and human monocytes were used as effector cells, and human or rabbit serum as the source of complement. Of all four effector cell types tested, mouse macrophages showed the highest cytotoxic activity, based on net cytotoxicity, minimum requirement for Mab concentration, and effector cell number. Different immunoglobulin classes were associated with characteristic patterns of reactivity with the various effector cells or complement, independent of the target cell type used. MAb able to mediate ADCC were found among all IgG subclasses, with IgG2a and IgG3 MAb inducing lysis with all effector cell types. IgM and IgA MAb were nonreactive in the various ADCC assays, but IgM MAb were highly cytotoxic with complement. |
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