Ductal Carcinoma Antigen: Characteristics, Tissue Distribution and Capacity to Represent a Target for Monoclonal Antibody Therapy

Abstract

Murine monoclonal antibody F36/22 was generated against the human breast carcinoma cell line MCF-7. The antibody reacts strongly with selected carcinoma cell lines and insignificantly against cell lines of mesenchymal derivation. No reactivity versus normal blood elements, bone marrow components or lymph nodes has been detected. Antigen is highly expressed in primary malignant tumors of ductal lineage to the virtual exclusion of lymphomas, sarcomas and non-ductal carcinomas, hence the designation Ductal Carcinoma Antigen. A small number of normal ductal structures also produce the antigen, although at greatly reduced levels. The antigen is found in the circulation of breast cancer patients where its exists as a high molecular weight glycoprotein. Purified antigen exhibits high density and a significant amount of carbohydrate content, thus resembling a mucin-like structure. The antibody-combining region also represents a carbohydrate component which is released upon alkaline-borohydride cleavage. The antigen behaves as an effective target in vitro for antibody dependent cytotoxicity as mediated both with complement and effector cells. Further, the passive administration of monoclonal antibody F36/22 results in a rapid decrease in the volume of human tumor xenografts as grown on athymic mice. The usefulness of this murine system as a pre-clinical model for human immunotherapies is under study.