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Interaction of Monoclonal Antibodies with Cell Surface Antigens of Human Ovarian Carcinomas¹

Divisions of Tumor Immunology [Y. M., R. C. B.], Medicine [R. C. B.], and Gynecological Oncology [R. C. K.], Dana-Farber Cancer Institute; the Departments of Medicine [R. C. B.] and Radiology [M. Z.], and Division of Gynecologic Oncology [R. C. K.], Brigham and Women's Hospital [R. C. K.]; and the Departments of Medicine [R. C. B.], Radiology [M. Z.], and Obstetrics and Gynecology [R. C. K.], Harvard Medical School, Boston, Massachusetts 02115

Two monoclonal antibodies, OC 125 and OC 133, bind to distinct determinants on the surface of human epithelial ovarian carcinoma cell lines. OC 125 and OC 133 recognize determinants on molecules with molecular weights greater than 200,000 and 80,000, respectively. When binding to four different cell lines was compared, apparent affinity constants for OC 125 ranged from 3.1 x 10⁹ to 6.0 x 10⁷ M^-1, whereas those for OC 133 ranged from 1.6 x 10⁹ to 8.5 x 10⁸ M^-1. An estimate of the number of antigenic determinants per cell ranged from 1.0 x 10⁷ to 2.8 x 10⁵ for OC 125 and from 4.0 x 10⁵ to 3.4 x 10⁴ for OC 133. Antigenic determinants recognized by OC 125 and OC 133 could be detected in spent culture medium. When radiolabeled OC 125 was incubated with each of four ovarian tumor cell lines, approximately 90% of the antibody remained bound to the tumor cell surfaces for more than 20 hr. Similar binding of OC 133 was observed with three of the four ovarian tumor cell lines. By contrast, >70% of OC 133 antibody was either shed or endocytosed after binding to OVCA 433 cells over the same period. Antigenic modulation was not induced by either antibody interacting with any of the four cell lines. These data suggest that antigen may be lost from the surface of human ovarian carcinoma cells by several different mechanisms and that antigen release is not inconsistent with binding of radiolabeled antibody to the tumor cell surface for prolonged periods.

¹ Supported in part by funds from the William P. Graves Ovarian Research Fund and the National Cancer Cytology Center.

² Visiting Investigator from Teijen, Ltd.

³ Scholar of the Leukemia Society of America, Inc. To whom requests for reprints should be addressed, at Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 12/ 2/83. Accepted 3/30/84.

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