Article Text

Download PDFPDF
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}sc.itc.keio.ac.jp

Abstract

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

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.