The human tumor colony-forming assay (HTCFA) is an in vitro test that has been used to predict the activity of anticancer drugs against a patient's tumor. We utilized the assay to analyze the antiproliferative effects of seven interferons (IFNs) against 40 human melanomas to determine which IFN had the greatest antiproliferative activity in this drug-resistant tumor. IFNs studied included recombinant IFN-α2; human lymphoblastoid IFN; IFN-α Cantell; native βRPMI; two recombinant IFNs-β; and recombinant IFN-γ. Growth was sufficient [>30 tumor colony-forming units (TCFU)/well] for assessing the antiproliferative effects of at least one IFN in 25 tumors (63%). A dose-response relationship was demonstrated by all IFNs in tumors in which some activity was observed (p ≤ 0.01). Individual melanomas differed in their sensitivities to the various IFNs. Overall, however, none of the IFNs was markedly more effective in antiproliferative effects than any other, although there was a trend toward IFN-βser having more potent antiproliferative properties when compared to IFN-α2 (p = 0.055). Twelve of 13 tumors exposed to combinations of IFN-βser and IFN-γ demonstrated a synergistic antiproliferative effect. In all but two of these, low concentrations of each IFN (≤50 U/ml), when combined, resulted in 85–95% inhibition. As prolonged exposure to high concentrations of IFN are often not clinically tolerable, these data suggest that IFN combinations may be one way of achieving more clinically meaningful IFN doses, schedules, and regimens, provided antiproliferative effects are of importance in vivo.
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