Mouse-human chimeric antibody against the multidrug transporter P-glycoprotein.
In an effort to devise an effective treatment for human drug-resistant cancers, we have generated a monoclonal antibody, MRK16, reactive to the multidrug transporter P-glycoprotein. The monoclonal antibody inhibited the growth of human drug-resistant tumor cells in a xenograft model, suggesting its potential usefulness in the immunotherapy of drug-resistant cancers. In this study, we have developed a recombinant chimeric antibody in which the antigen-recognizing variable regions of MRK16 are joined with the constant regions of human antibodies. When human effector cells were used, the chimeric antibody, MH162, was more effective in killing drug-resistant tumor cells than the all-mouse monoclonal MRK16. The chimeric antibody against the multidrug transporter P-glycoprotein will be a useful agent in immunotherapy of human drug-resistant cancers.
Hamada
H
H
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Miura
K
K
Ariyoshi
K
K
Heike
Y
Y
Sato
S
S
Kameyama
K
K
Kurosawa
Y
Y
Tsuruo
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D004351:Drug Resistance; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014162:Transfection / Q000276:immunology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins