目的 评价抗HER2 人源化抗体的急性毒性。方法 将食蟹猴随机分为4 组,包括溶媒对照和抗HER2 人源化抗体75、150 和250 mg/kg 组,单次iv 溶媒对照组或供试品,进行各项毒理学指标检测。结果 给药后各组动物临床症状、体质量、摄食量、体温、心电图、血压和血液学检测均未见明显异常;血清生化结果显示,150 mg/kg 组与250 mg/kg 组动物给药后血清IgG 水平出现一过性增加;各组动物均未见大体病理学改变。结论 食蟹猴单次iv 抗HER2 单抗,总体上动物具有良好的耐受性,最大耐受剂量可达250 mg/kg,这些结果为进一步临床前评价抗HER2 人源化单克隆抗体的安全性奠定了基础。

Objective To evaluate the single dose toxicity of a humanized anti-HER2 monoclonal antibody. Methods Cynomolgus monkeys were randomly divided into four groups: vehicle control, 75, 150, and 250 mg/kg. All animals were iv administered with a single-dose vehicle control or test article. Then a series of toxicological parameters were determined. Results Following a single iv injection with anti-HER2 monoclonal antibody, there were not obvious abnormalities in clinical symptom, food consumption, weight, temperature, electrocardiogram, blood pressure, and hematology analysis for all article-treated groups. A transient increase of serum IgG was observed in 150 and 250 mg/kg dosage groups. No macro-pathological change was found in all animals. Conclusion Single iv injection with anti-HER2 monoclonal antibody was well tolerated in cynomolgus monkeys. The maximum tolerated dose of anti-HER2 monoclonal antibody is greater than that of 250 mg/kg. These results will facilitate further preclinical safety studies of humanized anti-HER2 monoclonal antibody.

十二五“重大新药创制”科技重大专项(2012ZX09302001)