Evaluation of Long-Term Toxicity of Ad/hIFN-γ, an Adenoviral Vector Encoding the Human Interferon-γ Gene, in Nonhuman Primates

Interferon-γ(IFN-γ) plays an important role in the immunomodulation and growth inhibition of many tumor cells, but its clinical application is limited by its systemic toxicity. Ad/hIFN-γ, a nonreplicating adenoviral vector encoding human IFN-γ, has been reported to inhibit tumor growth in vitro and in a xenograft model. In this study, the long-term toxicity of Ad/hIFN-γ was assessed in cynomolgus macaques (Macaca fascicularis). Thirty animals were enrolled into 5 groups, and administered intramuscularly, respectively, Ad/hIFN-γ (3.3 × 1010, 3.3 × 1011, or 3.3 × 1012 VP/kg), Ad/LacZ (vector control, 3.3 × 1011 VP/kg), or excipient 3 times per week for 8 weeks, followed by a 4-week recovery period. At 12 weeks all experimental animals appeared generally healthy, and there were no statistically significant differences in body weight, urinalysis, hemogram, blood biochemistry, and electrocardiogram results between the treatment and control groups. No significant toxic effects were noted on macroscopic and micr...