Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells

Abstract

Four different human epithelial differentiation antigens (MT179, MW162, MW207, and MX35) have been defined by mouse monoclonal antibodies obtained from mice immunized with either an ovarian carcinoma cell line or fresh ovarian carcinoma cells. In an attempt to identify tissue-specific antigens restricted to ovarian epithelial cells, sections of a benign ovarian cyst were used as the initial target for screening hybridoma supernatants. The distribution of the antigens detected by these monoclonal antibodies was determined on frozen sections of 24 normal tissues and on 103 cultured cell lines of various histological types. In spite of the method used to select these monoclonal antibodies, they all reacted to some degree with normal epithelial cells in tissues other than ovary. All antibodies were unreactive with nonepithelial cells in frozen sections. These antibodies also reacted with frozen sections of most or all fresh ovarian carcinomas and benign ovarian cysts. All antibodies were unreactive with ABH, Lewis blood group-related antigens and appeared to be different in specificity from previously described well-characterized antigens of ovarian carcinoma cells. MW162 was characterized as a high-molecular-weight mucin-like molecule, and the determinant recognized is probably carbohydrate in nature. MW207 was identified as a Mr 37,000 protein. These monoclonal antibodies and 24 other previously derived antibodies that react with epithelial differentiation antigens were tested for reactivity with the surface of fresh ovarian carcinoma ascites cells and for nonreactivity with normal mesothelial cells. This assay was designed to select monoclonal antibodies that might be effective agents for i.p. therapy or radioimmunodetection of human ovarian carcinoma. Five antibodies with the desired specificity were selected; these were the four new antibodies described herein and MH99, which was characterized previously and recognizes a glycoprotein having Mr 38,000 and 29,000 subunits. The degree of heterogeneity of antigen expression on ascites carcinoma cell was dependent on the particular antigen being examined and was related to the biochemical nature of the antigen. In particular, most ABH and Lewis blood group-related antigens showed a striking degree of heterogeneity.