Monoclonal antibodies to breast cancer-associated antigens as potential reagents in the management of breast cancer.

Abstract

Monoclonal antibodies reactive with the surface of human breast carcinoma cells have been generated and characterized. The immunogens used were membrane-enriched fractions of metastatic carcinoma lesions. The various monoclonals were shown to react with previously known as well as with novel tumor-associated antigens (TAAs). The most specific of the latter group is monoclonal B72.3, which is reactive with a 220,000 to 400,000 high-molecular-weight glycoprotein complex found in 50% of human mammary carcinomas and 80% of human colon carcinomas. Monoclonal antibody B6.2, which recognizes a 90,000-d glycoprotein, was radiolabeled and shown to efficiently localize human carcinoma transplants in athymic mice via gamma imaging without the use of second antibody or background subtraction manipulations. F(ab')2 and Fab' fragments were shown to be more efficient for tumor localization than intact immunoglobulin. Whereas the phenomenon of antigenic heterogeneity of tumor cell populations has long been known to exist, this phenomenon was also shown to manifest itself as antigenic modulation, in which specific TAAs can modulate their expression on the cell surface concurrent with different phases of the cell cycle. A phenomenon known as antigen evolution, in which a specific cloned tumor cell population can gradually drift in antigenic phenotype, has also been demonstrated. Recombinant interferon has been employed to (1) enhance the expression of specific TAAs on the surface of tumor cells already expressing the antigen; and (2) induce the expression of specific TAAs on the surface of carcinoma cells not previously expressing the antigen. The clinical implications of such phenomena in gamma scanning for the detection of tumor masses and for tumor immunotherapy are discussed. Methods for circumvention of problems inherent in the clinical use of monoclonal antibodies are also addressed.