Preclinical safety evaluation of rAd5-hTERTC27 by intravenous injection

•We have prepared a replication defective adenovirus vector carrying hTERTC27.•Intravenous rAd5-hTERTC27 was well tolerated on rats at the experimental dose.•Intravenous rAd5-hTERTC27 was not toxic on monkeys at the experimental dose.•No hemolysis or systemic anaphylaxis were observed in the Ad5-hTERTC27 groups.•Effects on the central nervous system in mice were negative at the effective dose.

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 × 1011 VP/kg in rats and 9 × 1010 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 × 1011 VP/kg (p < 0.05) but not at lower doses of 2 × 1010 and 6 × 1010 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.