Differential in vitro effects of recombinant α-interferon and recombinant γ-interferon alone or in combination on the expression of melanoma-associated surface antigens

The effect of individual in vitro concentrations of recombinant α-interferon species A (rIFN-α-A), recombinant γ-interferon (rIFNγ), and combinations of both interferons on the expression of melanoma-associated surface antigens p97 and the high molecular weight proteoglycan (HWM- MAA-240K) as detected by monoclonal antibodies (MoAb) 96.5 and ZME 018 respectively, was examined. rIFN-α-A at optimal concentrations of 50 and 500 U/ml caused significant (p < 0.05 and p < 0.01, respectively) increases in expression of p97 on the melanoma cell line Hs 294t following a 48-h incubation. No change in 96.5 binding was noted with rIFN-α-A concentrations up to 1000 U/ml after a 24-h incubation. Likewise, rIFN-γ at an optimal concentration of 500 U/ml enhanced p97 expression slightly at 24 h (p = 0.053) and more significantly by 48 h at concentrations of 50, 500, and 1,000 U/ml (p < 0.01, p < 0.05, and p < 0.025, respectively). In contrast, neither rIFNγ nor rIFN-α-A had an effect on modulation of the HMW-MAA as detected by ZME 018, irrespective of dose or incubation time. Optimal and suboptimal concentrations of rIFN-α-A plus rIFN-γ in combination did not significantly enhance expression of either antigen to a greater extent than that observed with optimal concentrations of each IFN alone, despite the fact that the combination had a synergistic anti-proliferative effect. These data demonstrate that the effects of each interferon (IFN) on the expression of melanoma-associated antigens (MAA) are heterogeneous and depend on IFN type and concentration, exposure time, and characteristics of the antigen studied. Moreover, the data regarding combinations of rIFN-α-A and rIFN-γ suggest that mechanisms responsible for IFN effects on MAA modulation are independent from its effects on proliferation. These findings may have clinical relevance with respect to trials using combinations of α- and/or γ-IFN plus MoAb in vivo.