2006 Fiscal Year Final Research Report Summary
Establishment of molecular targeting therapy against ovarian cancer using human monoclonal antibody
| Project/Area Number |
17591759
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
SUZUKI Nao St. Marianna University, Medicine, Lecturer, 医学部, 講師 (90246356)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Daisuke Keio University, Medicine, Professor, 医学部, 教授 (30167788)
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| Project Period (FY) |
2005 – 2006
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| Keywords | ovarian cancer / molecular targeting therapy / CA125 / human monoclonal antibody / clear cell adenocarcinoma |
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| Research Abstract |
Objective : 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.
Methods : 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 ELISA 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 (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 mice with heterografts of RMG-I tumors.
Results : 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 kDa to 250 kDa. 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.
Conclusion : 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.
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