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目的:评价食蟹猴静脉重复给药抗CD20功能人源化单克隆抗体SM09的安全性。方法:将食蟹猴随机分为溶媒对照组,SM09低、高剂量组(25,50 mg.kg-1),每组6只,静脉注射给药,每周1次,连续8周,恢复期12周,进行各项毒理学指标检测。结果:除个别动物偶见呕吐外,体重、进食量、体温、尿、心电图、骨髓细胞计数等均未显示与供试品相关的改变。SM09给药后能够诱导动物产生快速深度的外周血B细胞清除,至恢复期结束,多数动物外周血中B细胞水平恢复正常。给药4周,动物血液白细胞及淋巴细胞下降,之后逐渐回升。给药结束时动物补体C4水平略有降低。组织病理学检查结果除药理学作用相关的改变外,未见其他与供试品相关的改变。结论:食蟹猴连续静脉注射SM09,总体上具有良好的剂量耐受性,除观察到与药理作用相关的效应外,未见其他毒性反应。
Objective: To evaluate the safety of repeated administration of anti-CD20 functional humanized monoclonal antibody SM09 in cynomolgus monkeys. Methods: The cynomolgus monkeys were randomly divided into vehicle control group, SM09 low and high dose group (25, 50 mg.kg-1), 6 rats in each group, administered intravenously once a week for 8 weeks Period of 12 weeks, the toxicological indicators of detection. RESULTS: Except individual vomiting, body weight, food intake, body temperature, urine, electrocardiogram, bone marrow cell count and so on did not show any changes related to the test substance. Administration of SM09 induced rapid peripheral clearance of B cells in animals, until the end of convalescence, and the levels of B cells in peripheral blood of most animals returned to normal. Four weeks after administration, the blood leukocytes and lymphocytes in the animals decreased, and then gradually rose. Animal complement C4 levels slightly decreased at the end of dosing. Histopathological findings In addition to the changes associated with pharmacological effects, no other changes related to the test product were observed. CONCLUSIONS: Cynomolgus monkeys injected with SM09 intravenously for a sustained period had generally good dose tolerability. No toxic effects were observed except for the effects associated with pharmacological effects.