An analog of human alpha-and beta-
interferons (IFN-alpha and -beta) (generally consisting of the most frequently observed
amino acid residue at each position in the molecule) has pronounced
antiviral and antiproliferative activity in human and hamster cells. Intraperitoneal administration of this analog (designated
IFN-alpha Con 1) to hamsters
at 10(6) to 10(8) U/kg resulted in proportional increases in plasma concentrations through 6 h of monitoring.
IFN-alpha Con 1 at these doses effectively limited encephalomyocarditis virus (EMCV)
infections of hamsters. A natural human IFN-alpha preparation was also active against
virus infections in hamsters. The antitumor activity of
IFN-alpha Con 1 and natural human IFN-alpha was assessed in hamsters inoculated with lethal TBD932
lymphosarcoma. Various IFN treatment schedules resulted in prolonged survival following
tumor challenge.
IFN-alpha Con 1 administered
at 10(5) to 10(6) U/hamster daily for 9-12 days following
tumor challenge was effective in delaying
tumor development, as was a natural human IFN-alpha preparation. The efficacies of combined IFN and
cyclophosphamide therapies were determined. Unlike the natural human subtype IFN-alpha A,
IFN-alpha Con 1 did not diminish the efficacy of
cyclophosphamide (2.5 mg/hamster for 3 days) against the
lymphosarcoma. However, an ineffective dose of
cyclophosphamide (0.05 mg/hamster for 3 days) when combined with
IFN-alpha Con 1 treatment showed enhanced antitumor activity. Combinations of
cimetidine (16 mg/hamster for 4 days) and
IFN-alpha Con 1 treatment did not prolong survival in this model system.