Monoclonal Anti‐P‐glycoprotein Antibody‐dependent Killing of Multidrug‐resistant Tumor Cells by Human Mononuclear Cells

Mouse monoclonal antibodies (MRK16 and MRK17) against human multidrug‐resistant cancer cell lines were tested for antibody‐dependent cytotoxicity mediated by human blood mononuclear cells, using a 4‐h (51)Cr release assay. MRK16 (IgG(28) isotype) was shown to be more effective than MRK17 (IgG(1) isotype). Moreover, when four pairs of drug‐resistant and their parent sensitive human cancer cells were tested for antibody‐dependent cell‐mediated cytolysis (ADCC) using MRK16, only the drug‐resistant cell lines were susceptible to ADCC reaction. When highly purified lymphocytes (>99%) and monocytes (>97%) were isolated from blood mononuclear cells by centrifugal elutriation and adherence, MRK16 promoted both lymphocyte‐ and monocyte‐mediated tumor cell killing, whereas MRK17 induced only a lymphocyte‐mediated ADCC reaction. These results suggest that MRK16 of IgG(28) subtype may be a useful therapeutic agent in eradication of drug‐resistant cancer cells expressing P‐glycoprotein through ADCC reaction.