The objective of this research is to develop more effective diagnostic approaches to human breast cancer using monoclonal antibodies (MAb) reactive with breast carcinoma-associated antigens. We have developed a panel of MAbs, designated the DF series, prepared against membrane enriched fractions of a metastatic human breast carcinoma and MCF-7 cells. One of these, MAb DF3, has been further characterized and shown to recognize an antigen with an M?r? of 300 kilodalton. The DF3 antigen is detectable on the surface of human breast carcinoma cells and immunoperoxidase staining with MAb DF3 clearly distinguishes malignant and benign breast lesions. Double-determinant immunometric assays have been developed to monitor circulating DF3 antigen levels in patients with breast cancer. DF3 levels were elevated in 70% of patients with metastatic breast cancer. In contrast, only 6% of healthy women and less than 2% of patients with prior breast cancer who were free of disease after treatment had elevated DF3 antigen levels. Furthermore, DF3 antigen levels were shown to reflect changes in the clinical course of eight patients with metastatic breast cancer. The further evaluation of MAb DF3 in immunodiagnostic approaches to human breast cancer requires a more precise understanding of the immunochemical characteristics of DF3 antigen and factors affecting its expression. This work should provide the basis for effectively using MAb DF3 in determining the prognostic value of immunoperoxidase studies in primary human breast carcinomas and in monitoring clinical course by the radioimmunometric plasma assays. A third immunodiagnostic approach will involve the use of radioiodinated MAb DF3 in lymphoscintigraphy studies to monitor for breast cancer involvement in axillary and internal mammary lymph nodes. The remaining MAbs in the DF series (DF4, 7, 9, 15, 16) will be evaluated for: (1) immunoperoxidase staining of fixed tissue slides; (2) evaluation of the immunochemical properties, stability, affinity and cell surface expression of the DF antigens; (3) circulation of the DF antigens and correlation with the clinical status in patients with breast cancer; and (4) utility of the DF MAbs for radioimaging studies. (2)
| Abe, M; Kufe, D (1993) Characterization of cis-acting elements regulating transcription of the human DF3 breast carcinoma-associated antigen (MUC1) gene. Proc Natl Acad Sci U S A 90:282-6 |
| Maimonis, P; Hayes, D F; Schaffel, S et al. (1991) Lung cancer-associated protein: development and characterization of a new assay that detects a circulating lung cancer marker. Cancer Res 51:3838-42 |
| Maimonis, P; Hayes, D F; O'Hara, C et al. (1990) Detection and characterization of a high molecular weight human lung carcinoma-associated glycoprotein. Cancer Res 50:6738-43 |
