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.
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.
Suzuki
N
N
Department of Obstetrics and Gynecology, St. Marianna University, School of Medicine, Kanagawa, Japan.
Tamada
Y
Y
Shigirahara
K
K
Suzuki
A
A
Susumu
N
N
Ishida
I
I
Aoki
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen