Mouse-Human Chimeric Antibody MH171 against the Multidrug Transporter P-Glycoprotein

Abstract

We have developed a mouse‐human chimeric antibody MH171, in which the antigen‐recognizing variable regions of the mouse monoclonal antibody MRK17 are joined with the constant regions of human IgG1 antibodies. The MRK17 recognizes specifically the multidrug transporter P‐glycoprotein and inhibits the growth of human multidrug resistant (MDR) tumor cells in vitro and in the xenograft nude mouse model system. The established chimeric MH171 antibody forms an apparently intact IgG composed of heavy and light chains covalently assembled via disulfide bonds in sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and is specific to MDR cell lines with a similar affinity to the original mouse MRK17. MH171 also displays strong antibody‐dependent cell‐mediated cytotoxicity to the target cells in vitro, when human mononuclear cells are used as effector cells. The chimeric antibody against P‐glycoprotein, MH171, should be a useful agent in the treatment of human drug‐resistant tumors.