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Enhanced Expression of Surface Tumor-associated Antigens on Human Breast and Colon Tumor Cells after Recombinant Human Leukocyte -Interferon Treatment

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH [J. W. G., P. H. H., J. S.] and Office of Biologics, National Center for Drugs and Biologics, Food and Drug Administration [P. N.], Bethesda, Maryland 20205; Department of Microbiology, Cancer Center/Institute of Cancer Research, Columbia University, College of Physicians and Surgeons, New York, New York 10032 [P. B. F.]; and Roche Institute of Molecular Biology, Nutley, New Jersey 07110 [S. P.]

Treatment of human breast or colon carcinoma cells with recombinantly derived human leukocyte (clone A) interferon (IFN- A) increases the surface expression of specific tumor-associated antigens (TAAs) recognized by monoclonal antibodies (MAbs). The MAbs used, B1.1, B6.2, and B72.3, recognize three distinct TAAs, i.e., the M_r 180,000 carcinoembryonic antigen, a M_r 90,000, and a M_r 220,000 to 400,000 glycoprotein, respectively. The binding of the MAbs to the surface of tumor cells increased in a dose-dependent manner, with optimal levels of TAA enhancement at 100 to 1,000 units IFN- A/ml. Higher concentrations of IFN- A that were cytostatic or cytotoxic were also less effective in enhancing TAA expression. Human melanoma (A375) cells and normal fibroblasts (WI-38 and Flow 4000) do not express any of the three TAAs, either before or after interferon treatment. The ability of IFN- A to increase the expression of TAAs on human carcinoma cells was also temporally dependent, with optimal enhancement occurring after 16 to 24 hr. The enhancement of specific TAAs at the surface of the carcinoma cells by IFN- A was confirmed, using fluorescence-activated cell sorter analysis. These data demonstrate that the IFN- A-mediated increase of surface antigen is a result of both an accumulation of more antigen per cell, and an increase in the percentage of cells expressing the antigen. The ability of recombinant interferon to enhance specific TAAs on human carcinoma cells may be exploited in designing protocols for the in situ detection and therapy of human carcinoma lesions by MAbs, as well as in further defining the role of specific TAAs in the expression of the transformed phenotype.

¹ To whom requests for reprints should be addressed, at Laboratory of Tumor Immunology and Biology, Building 10, Room 8B07, National Cancer Institute, NIH, Bethesda, MD 20205.

Received 2/10/84. Accepted 4/25/84.

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