INTERACTION OF MONOCLONAL-ANTIBODIES WITH CELL-SURFACE ANTIGENS OF HUMAN OVARIAN CARCINOMAS

Abstract

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 MW > 200,000 and 80,000, respectively. When binding to 4 cell lines was compared, apparent affinity constants for OC 125 ranged from 3.1 .times. 109 to 6.0 .times. 107 M-1, whereas those for OC 133 ranged from 1.6 .times. 109 to 8.5 .times. 108 M-1. An estimate of the number of antigenic determinants per cell ranged from 1.0 .times. 107 to 2.8 .times. 105 for OC 125 and from 4.0 .times. 105 to 3.4 .times. 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 4 ovarian tumor cell lines, .apprx. 90% of the antibody remained bound to the tumor cell surfaces for > 20 h. Similar binding of OC 133 was observed with 3 of the 4 ovarian tumor cell lines. By contrast, > 70% of OC 133 antibody was 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 4 cell lines. These data suggest that antigen may be lost from the surface of human ovarian carcinoma cells by several mechanisms and that antigen release is not inconsistent with binding of radiolabeled antibody to the tumor cell surface for prolonged periods.