The safety of rAd5-hTERTC27, a replication defective adenovirus vector carrying hTERTC27 for possible use against hepatocellular carcinoma (HCC) was assessed. In single-dose evaluations, intravenous dose levels of up to 2×10(11)VP/kg in rats and 9×10(10)VP/kg in monkeys were well tolerated with no abnormal changes in general signs, body weight and food consumption, and no significant differences in biochemical parameters, urinalysis, ECG, and systemic necropsy observations between the rAd5 groups and solvent control group except that slight hematological change was observed. No hemolytic effect using rabbit blood, local perivasculitis following intravenous injection in rabbits or systemic anaphylaxis in guinea pigs following intravenous dosing was seen. No effects on the central nervous system of mice occurred following intravenous dosing with the exception of an increase in sleep duration at the dose of 1.2×10(11)VP/kg (p<0.05) but not at lower doses of 2×10(10) and 6×10(10)VP/kg in the hypnotic synergism test. These results demonstrate that administration of rAd5-hTERTC27 was well tolerated in an initial set of safety studies as part of an evaluation to allow human trials for the treatment of HCC.
Keywords: Gene therapy; HCC; Preclinical evaluation; Single-dose toxicity; hTERTC27.
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