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. 2007 Mar;18(3):207-21.
doi: 10.1089/hum.2006.149.

Long-Term Toxicity Studies in Canine of E10A, an Adenoviral Vector for Human Endostatin Gene


Long-Term Toxicity Studies in Canine of E10A, an Adenoviral Vector for Human Endostatin Gene

Bi-Jun Huang et al. Hum Gene Ther. .


E10A, a recombinant adenovirus type 5 vector carrying the human endostatin gene, may be a promising gene therapy drug in the treatment of solid tumors by antiangiogenesis, but a preclinical safety evaluation of E10A has not yet been performed. With high and low doses equivalent to 30 and 7.5 times the human curative dose, respectively, intramuscular injections of E10A were given once daily, 6 days/week, for 3 months, followed by a 1-month recovery period. As of 4 months, all experimental animals appeared generally healthy: normal behavior and eating habits, no nausea, vomiting, or salivation, no abnormal changes in urination or defecation, and increased body weight with the time of experiment. Urinalysis, hemogram, blood biochemistry, electrocardiogram, macroscopic and microscopic studies of organs and tissues were done before treatment, at month 3 of treatment, and 1 month posttreatment. At all time points, no significant abnormal toxic effects were noted. Preliminary investigation of E10A immunotoxicity in dogs indicated that anti-adenoviral antibodies were generated, in a dose- and time-independent manner, after E10A injection. Our data demonstrated that, long term, high-dose intramuscular administration of recombinant human endostatin-carrying adenovirus (E10A) was not notably toxic and might be safe for clinical therapeutic use, although additional long-term toxicity studies by other administration routes are still necessary.

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