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.