Expression behavior of 85-kDa membrane protein in adriamycin-resistant tumor cells and the inhibition of human tumor growth in athymic mice by MRK-20 monoclonal antibody against the protein.
Treatment of tumors with monoclonal antibodies against tumor antigen is one of the selective modalities for cancer therapy. We examined the therapeutic effect of MRK-20 (IgG1), a murine monoclonal antibody against resistance-associated 85-kDa membrane protein. The 85-kDa protein is expressed on the surface of multidrug-resistant cells induced by adriamycin. This protein is also expressed in some multiple-drug-resistant cells, including atypical multidrug-resistant cells. The protein, once lost during long-term culture without adriamycin, was rapidly induced by treatment with adriamycin but not with vinblastine or etoposide, suggesting a close relationship of the protein with adriamycin resistance but not with multidrug resistance. The antibody MRK-20 suppressed the growth of subcutaneously implanted tumors expressing the 85-kDa protein. Adriamycin-resistant human ovarian tumor 2780AD and innately resistant human erythroleukemia HEL cells in athymic mice were completely cured by treatment with MRK-20 antibody when the antibody was administered i.v. 2 days after s.c. tumor implantation. On the other hand, MRK-20 did not show any effect on the growth of the 85-kDa protein-negative A2780 human ovarian tumor. These results indicate that the effect of MRK-20 is highly specific to cells expressing 85-kDa protein.
Ishii
S
S
Institute of Molecular and Cellular Biosciences, University of Tokyo.
Naito
M
M
Tsuruo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D004915:Leukemia, Erythroblastic, Acute / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007074:Immunoglobulin G; D004317:Doxorubicin