Binding and cytotoxicity characteristics of the bispecific murine monoclonal antibody 2B1

• Published in: The Journal of immunology (1950) Vol. 151; no. 5; pp. 2877 - 2886
• Main Authors: Weiner, LM, Holmes, M, Richeson, A, Godwin, A, Adams, GP, Hsieh-Ma, ST, Ring, DB, Alpaugh, RK
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.09.1993; American Association of Immunologists
• Subjects: Animals; Antibodies, immunoglobulins; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibody Specificity; Antigens, Neoplasm - immunology; Biological and medical sciences; Cytotoxicity, Immunologic; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunoglobulin G - immunology; Killer Cells, Lymphokine-Activated - immunology; Mice; Molecular immunology; Monoclonal antibodies; Proto-Oncogene Proteins - genetics; Proto-Oncogenes; Receptor, ErbB-2; Receptors, IgG - analysis; Tumor Cells, Cultured; Antigen; Effectory cell; Vertebrata; Specificity; Mammalia; Mouse; Rodentia; Cytotoxicity; Monoclonal antibody; Bispecific antibody; Cell surface; Tumor cell
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.151.5.2877

Bispecific monoclonal antibodies (BsmAb) with specificity for tumor Ag and effector cell trigger molecules have been shown to redirect the cytotoxicity of several peripheral blood mononuclear cell populations against relevant tumor. The BsmAb, 2B1, binds to the extracellular domain of the c-erbB-2 gene product of the HER2/neu proto-oncogene and to CD16. In this report, the binding and cytotoxic characteristics of 2B1 are presented. Maximal saturation binding of 2B1 to PBL and c-erbB-2 expressing SK-OV-3 cells occurred in the 1 microgram/ml concentration range. However, substantial lysis potentiation was observed at 1000-fold lower BsmAb concentrations. Optimal tumor lysis was obtained when the BsmAb, PBL, and target cells were continuously coincubated. When PBL were franked with 2B1, washed, and added to labeled targets, substantially less lysis was observed. These results suggest that the best way to therapeutically exploit the cytotoxic attributes of 2B1 may be to obtain continuous BsmAb exposure to tumor. Approaches based on franking of this BsmAb to PBL may not be warranted.