Differential in vitro effects of recombinant alpha-interferon and recombinant gamma-interferon alone or in combination on the expression of melanoma-associated surface antigens.
The effect of individual in vitro concentrations of recombinant alpha-interferon species A (rIFN-alpha-A), recombinant gamma-interferon (rIFN gamma), 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-alpha-A at optimal concentrations of 50 and 500 U/ml caused significant (p less than 0.05 and p less than 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-alpha-A concentrations up to 1000 U/ml after a 24-h incubation. Likewise, rIFN gamma 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 less than 0.01, p less than 0.05, and p less than 0.025, respectively). In contrast, neither rIFN gamma nor rIFN-alpha-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-alpha-A plus rIFN gamma 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-alpha-A and rIFN gamma 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 alpha- and/or gamma-IFN plus MoAb in vivo.
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004347:Drug Interactions; D006801:Humans; D007167:Immunotherapy; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014407:Tumor Cells, Cultured / Q000276:immunology
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007370:Interferon Type I; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D007371:Interferon-gamma