期刊
HUMAN GENE THERAPY
卷 19, 期 8, 页码 827-839出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2007.180
关键词
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资金
- National Basic Research Program of China (973 Program) [2004CB518801]
- National High Technology Research and Development Program of China [2006AA2Z0489, 2007AA021202]
- Key Research Program of Guangdong Province, China [2003A10902]
- Medical Research Program of Guangdong Province, China [A2007219]
Interferon-gamma (IFN-gamma) 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-gamma, a nonreplicating adenoviral vector encoding human IFN-gamma, has been reported to inhibit tumor growth in vitro and in a xenograft model. In this study, the long-term toxicity of Ad/hIFN-gamma was assessed in cynomolgus macaques (Macaca fascicularis). Thirty animals were enrolled into 5 groups, and administered intramuscularly, respectively, Ad/hIFN-gamma (3.3 x 10(10), 3.3 x 10(11), or 3.3 x 10(12) VP/ kg), Ad/LacZ (vector control, 3.3 x 10(11) 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 microscopic examinations of organs and tissues. Preliminary investigation of the immunotoxicity of Ad/IFN-gamma indicated that anti-adenoviral and anti-hIFN-gamma antibodies were generated. These data demonstrate that long-term, high-dose intramuscular administration of Ad/IFN-gamma was not notably toxic and might be safe for clinical therapeutic use.
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