Potential Clinical Application of a Monoclonal Antibody to a Tumor Associated Glycoprotein (TAG-72)

Monoclonal antibody (MAb) B72.3, generated using a membrane-enriched fraction of cells from a mammary carcinoma metastasis, recognizes a high molecular weight glycoprotein complex of approximately 220,000 to 400,000d, termed TAG (Tumor-Associated Glycoprotein) 72 (1,2). MAb B72.3 has a high degree of selective reactivity for human breast carcinomas versus normal adult tissues. For example, using the immunoperoxidase technique on formalin-fixed tissue sections and radioimmunoassays on cell extracts, MAb B72.3 reacts with approximately 40–46% of primary breast carcinomas and 62% of metastatic breast lesions while no reactivity was observed with a variety of normal human tissue. Ninety-four percent of effusion specimens from breast cancer patients contained tumor cells which express TAG-72, while no reactivity of MAb B72.3 was observed with mesothelial cells or macrophages in benign or malignant effusions. Analysis of the reactivity of MAb B72.3 to sections of formalin-fixed breast carcinomas and to the MCF-7 breast carcinoma cell surface demonstrated heterogeneity of expression of TAG-72. Treatment of MCF-7 cells with recombinant human leukocyte interferon (IFN-alpha A) enhanced the detection of TAG-72 in a dose-dependent manner, and reduced the amount of 125I-labeled MAb B72.3 required to bind 1000 cpm to MCF-7 cells by more than 20-fold. The results demonstrate a highly specific tumor antigen which is expressed selectively on human carcinoma cells versus adult normal tissue. Furthermore, these results indicate that (a) MAb B72.3 can be used to detect occult adenocarcinoma cells in human tissues and (b) biological response modifiers, such as IFN-alpha A may be used to alter the tumor cell surface antigenic phenotype and perhaps enhance the utility of MAb B72.3 in the immunodetection and therapy of breast cancer.