Antiviral and Antitumor Effects of a Human Interferon Analog, IFN-αCon1, Assessed in Hamsters

Abstract

An analog of human α- and β-interferons (IFN-α and -β) (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-αCon₁) to hamsters at 10⁶ to 10⁸ U/kg resulted in proportional increases in plasma concentrations through 6 h of monitoring. IFN-αCon₁ at these doses effectively limited encephalomyocarditis virus (EMCV) infections of hamsters. A natural human IFN-α preparation was also active against virus infections in hamsters. The antitumor activity of IFN-αCon₁ and natural human IFN-α was assessed in hamsters inoculated with lethal TBD932 lymphosarcoma. Various IFN treatment schedules resulted in prolonged survival following tumor challenge. IFN-αCon₁ administered at 10⁵ to 10⁶ U/hamster daily for 9-12 days following tumor challenge was effective in delaying tumor development, as was a natural human IFN-α preparation. The efficacies of combined IFN and cyclophosphamide therapies were determined. Unlike the natural human subtype IFN-αA, IFN-αCon₁ 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-αCon₁ treatment showed enhanced antitumor activity. Combinations of cimetidine (16 mg/hamster for 4 days) and IFN-αCon₁ treatment did not prolong survival in this model system.