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A New Tumor-associated Antigen Expressed on Breast Carcinomas, Defined by Monoclonal Antibody BCA 227¹

INSERM U.211, Faculté de Médecine, 44035 Nantes Cedex, France [H. M. B., S. P., J. A., M. K., P. T., C. S-M., J-Y. D., J-F. C.]; Laboratoire d'Immunologie Moléculaire, Faculté de Pharmacie, Nantes, France [J. A.]; and Centre René Gauducheau, Quai Moncousu, Nantes, France [P. T., J-Y. D., J-F. C.]

After immunization of mice with the human breast carcinoma cell line MCF-7, we produced monoclonal antibody (mAb) BCA 227, which allowed us to characterize a new tumor-associated antigen. This molecule is strongly expressed by well differentiated mammary carcinoma cell lines and by some other tumor cell lines of epithelial origin. Immunohistological study of frozen sections of different tissues and tumors confirmed its expression by tumor cells of epithelial origin, particularly infiltrating duct carcinomas of the breast. The antigen is also expressed, to a lesser extent, by some normal epithelial cells. Its biochemical characterization revealed a M_r 71,000 protein without an N-linked sugar moiety. Six to 40 x 10³ binding sites are present on breast tumor cell surfaces. Although mAb BCA 227, which was found to be of the IgG2a isotype, did not mediate antibody-dependent cell-mediated cytotoxicity with either human or mouse effector cells, a 50% inhibition of SK-BR5 tumor growth was obtained in nude mice, suggesting that another mechanism is responsible for this inhibition. Biodistribution studies of radiolabeled F(ab')₂ fragments of mAb BCA 227 in tumor-bearing nude mice showed a preferential localization in the tumor. All these data are in favor of the use of mAb BCA 227 as an immunodiagnostic tool for breast cancer.

¹ This work was supported by Association pour la Recherche sur le Cancer (ARC), Villejuif, France, and Association Nationale de Valorisation de la Recherche (ANVAR), France.

² To whom requests for reprints should be addressed, at INSERM U.211, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex, France.

Received 4/16/90. Accepted 12/13/90.