Binding and cytotoxicity characteristics of the bispecific murine monoclonal antibody 2B1.
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.
Weiner
L M
LM
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Holmes
M
M
Richeson
A
A
Godwin
A
A
Adams
G P
GP
Hsieh-Ma
S T
ST
Ring
D B
DB
Alpaugh
R K
RK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D051379:Mice; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG / Q000032:analysis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; C000715470:MAS1 protein, human