ENHANCED EXPRESSION OF SURFACE TUMOR-ASSOCIATED ANTIGENS ON HUMAN-BREAST AND COLON-TUMOR CELLS AFTER RECOMBINANT HUMAN-LEUKOCYTE ALPHA-INTERFERON TREATMENT

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (8) , 3208-3214
Abstract
Treatment of human breast or colon carcinoma cells with recombinantly derived human leukocyte (clone A) interferon (IFN-.alpha. A) increases the surface expression of specific tumor-associated antigens (TAA) recognized by monoclonal antibodies (MAb). The MAb used, B1.1, B6.2 and B72.3, recognize 3 distinct TAA, i.e., the MW 180,000 carcinoembryonic antigen, a MW 90,000 and a MW 220,000-400,000 glycoprotein, respectively. The binding of the MAb to the surface of tumor cells increased in a dose-dependent manner, with optimal levels of TAA enhancement at 100-1000 U IFN-.alpha. A/ml. Higher concentrations of IFN-.alpha. 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 3 TAA, either before or after interferon treatment. The ability of IFN-.alpha. A to increase the expression of TAA on human carcinoma cells was also temporally dependent, with optimal enhancement occurring after 16-24 h. The enhancement of specific TAA at the surface of the carcinoma cells by IFN-.alpha. A was confirmed, using fluorescence-activated cell sorter analysis. The IFN-.alpha. 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 TAA on human carcinoma cells may be exploited in designing protocols for the in situ detection and therapy of human carcinoma lesiomns by MAb, as well as in further defining the role of specific TAA in the expression of the transformed phenotype.