Generation of monoclonal antibodies to human milk-fat globule membrane antigens, with special reference to a precipitable secretory product of breast and ovarian carcinomas.

Monoclonal antibodies were generated against protein antigens extracted from human milk-fat globule (HMFG) membranes. Of more than 500 hybridoma clones, 16 secreted antibodies reacting with breast and ovarian carcinoma cells, but not with lymphocytes or macrophages. Five clones were further expanded and characterized; four reacted with plasma membranes of all breast and ovarian carcinomas rested, but also with normal breast. One of the monoclonal antibodies, III D 5, reacted mainly against the cytoplasmic components of breast cancer cells, whereas the reaction with normal or mastopathic breast was against the luminal plasma membranes. The antigen recognized by the antibody was secreted in ascites fluid or pleural effusions of patients with widely spread ovarian or breast carcinomas, and could be demonstrated by immunodiffusion. It is suggested that the antigen is composed of several glycoprotein subunits bearing the same repetitive epitope. This might be the physicochemical basis for its precipitability with a monoclonal antibody.