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

Abstract

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.