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HMOCC-1, a human monoclonal antibody that inhibits adhesion of ovarian cancer cells to human mesothelial cells
Authors:Suzuki Nao  Aoki Daisuke  Tamada Yutaka  Susumu Nobuyuki  Orikawa Kimiko  Tsukazaki Katsumi  Sakayori Motoko  Suzuki Atsushi  Fukuchi Takeshi  Mukai Makio  Kojima-Aikawa Kyoko  Ishida Isao  Nozawa Shiro
Affiliation:Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. naos@sc.itc.keio.ac.jp
Abstract:OBJECTIVES: Ovarian carcinoma is one of the most common gynecologic cancers and shows the worst prognosis since current therapies are not sufficiently effective at achieving and maintaining remission. To develop new treatment, a monoclonal antibody recognizing human ovarian cancer cells was raised in KM mice. METHODS: A human monoclonal antibody targeting RMG-I (an ovarian carcinoma cell line) was established with hybridomas of myeloma cells and spleen cells from KM mice. The immunohistochemical reactivity of various types of ovarian carcinoma and other tumors was investigated. RMG-I cells were treated with N-glycosidase F, NaOH, H(2)SO(4), and Gal NAC-alpha-benzyl to investigate the target antigens by Western blotting. The effect of HMOCC-1 on adhesion of RMG-I cells to cultured human mesothelial cells was also investigated. RESULTS: The new human monoclonal antibody, HMOCC-1, was an immunoglobulin M that recognized ovarian epithelial carcinoma. Immunohistochemical staining revealed HMOCC-1 positivity in 83.2% of ovarian carcinomas. The antigen recognized by HMOCC-1 was apparently a glycoprotein since Western blotting yielded a broad band (34.8-49.1 kDa). HMOCC-1 inhibited the attachment of RMG-I cells to monolayers of cultured peritoneal mesothelial cells in a concentration-dependent manner. CONCLUSIONS: This new human monoclonal antibody reacted with most ovarian cancers tested. The antigen recognized by HMOCC-1 is a glycoprotein located on the cell membrane. Inhibition of the attachment of RMG-1 cells to mesothelial cells by HMOCC-1 suggests a potential role for this antibody in the treatment of ovarian cancer.
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