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Human monoclonal antibody for ovarian clear cell carcinoma-2, a human monoclonal antibody with antitumor activity against ovarian cancer cells that recognizes CA125-like antigen
  1. N. Suzuki*,
  2. Y. Tamada,
  3. K. Shigirahara,
  4. A. Suzuki,
  5. N. Susumu,
  6. I. Ishida and
  7. D. Aoki
  1. * Department of Obstetrics and Gynecology, St. Marianna University, School of Medicine, Kanagawa, Japan;
  2. Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan; and
  3. Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd, Gunma, Japan
  1. Address correspondence and reprint requests to: Daisuke Aoki, MD, Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. Email: aoki{at}


In recent years, antibody therapy employing monoclonal antibodies has become a new approach for treating cancer. This study was performed to establish a human monoclonal antibody recognizing an epitope related to CA125 using KM mice and to assess its reactivity with ovarian cancer cells. A human ovarian clear cell adenocarcinoma cell line (RMG-I) was used to immunize KM mice, and hybridoma supernatant was obtained by a standard method employing enzyme-linked immunosorbent assay screening. Next, selection of hybridomas was performed with two antibodies (MA602-1 and MA602-6) and a sandwich immunoassay for CA125-like antigen, and then the limiting dilution was used to obtain a human monoclonal antibody. Immunohistochemical reactivity of this antibody (human monoclonal antibody for ovarian clear cell carcinoma-2 [HMOCC-2]) with ovarian cancer was assessed, while its specificity was analyzed by Western blotting. Various antibodies were used to identify the epitope targeted by HMOCC-2. Finally, the antitumor effect of HMOCC-2 was assessed by intraperitoneal administration to SCID (severe combined immunodeficiency) mice with heterografts of RMG-I tumors. HMOCC-2 showed a positive reaction with 60% (63/105) of ovarian cancer specimens. Western blotting of the membrane fraction of RMG-I revealed several bands at 120–250 kd. HMOCC-2 recognized the CA125-like antigens identified by several antibodies. HMOCC-2 also exhibited significant antitumor activity (P< 0.01) against ovarian cancer heterografts. HMOCC-2 reacts specifically with ovarian cancer cells via a target epitope analogous to that of CA125 and also exhibits activity against ovarian tumors. These findings suggest that it may have the potential to be employed clinically for molecular-targeting therapy.

  • clear cell adenocarcinoma
  • human monoclonal antibody
  • molecular-targeting therapy
  • ovarian cancer
  • RMG-1 cells

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