MODULATION OF TUMOR-ASSOCIATED ANTIGEN EXPRESSION ON HUMAN PANCREATICAND PROSTATE CARCINOMA-CELLS IN-VITRO BY ALPHA-INTERFERON AND GAMMA-INTERFERON

Interferons (IFNs) are known to have antiviral effects and have been s hown to enhance the expression of tumor-associated antigens (TAA) on d ifferent target cells. In our current study, we investigated the poten tial of IFN-alpha or IFN-gamma to enhance the expression of the TAAs r ecognized by monoclonal antibodies (MAbs) 19-9, B72.3, 17-1A, and BR55 -2 on pancreatic cancer cell lines and the potential of IFN-gamma to m odulate the expression of a single TAA, BR55-2, on nonpancreatic cance r cell lines. Expression of these TAAs, percentage of positive cells a nd mean fluorescence intensity, was measured by now cytometry. In thes e studies, we provide evidence that one prostate (DU 145) and two panc reatic (HPAF and BxPC-3) cancer cell lines that moderately express BR5 5-2 can be upregulated by IFN-gamma treatment, with optimal enhancemen t occurring between 48 and 72 h with 1,000 IU/ml. Cell lines that high ly expressed BR55-2 could not be further upregulated by the doses of I FNs tested during the various periods used. IFN-alpha or IFN-gamma tre atments did not significantly change the levels of TAA expression on p ancreatic cancer cell lines that bound MAbs 17-1A or 19-9. Cell lines that did not bind MAbs 17-1A, 19-9, B72.3, or BR55-2 before IFN treatm ents could not be induced to express these antigens after treatment. A lthough antigen expression does not ensure detectable therapeutic bene fit, increased antigen expression on tumor tissues may augment the eff icacy of MAbs bearing radionuclides, toxins, or effector cells to the tumor site. In each of these situations, the use of IFNs to enhance TA A expression, particularly IFN-gamma, may merit consideration.