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抗体偶联药物S037的免疫毒性研究

发表时间:2018-12-14  浏览量:94  下载量:4
全部作者: 鲁静,李建祥,张雪峰
作者单位: 苏州大学医学部公共卫生学院;江苏鼎泰药物研究股份有限公司
摘 要: 目的:抗体偶联药物(antibody-drug conjugate,ADC)S037重复静脉输注给予食蟹猴,观察其免疫毒性相关指标的变化,为安全性评价提供科学依据。方法:采用3~5岁食蟹猴40只,随机分成4组,每组10只,雌雄各半。溶媒对照组给予0.9%氯化钠注射液,S037低、中、高剂量组的剂量分别为0.6,2,10 mg/kg. 静脉输注8个周期(每3周给药1次为1个给药周期),停药恢复6周。免疫毒性评价指标包括血液学(白细胞、白细胞分类百分比及计数)、血清生化(总蛋白、白蛋白、白/球比)、免疫器官大体解剖、脏器重量(胸腺、脾脏)、组织学检查(胸腺、脾脏、颌下淋巴结、肠系膜淋巴结)和骨髓涂片、免疫球蛋白(IgG、IgA、IgM)、补体(C3 和C4)、循环免疫复合物(circulating immune complex,CIC)和淋巴细胞分群。结果:食蟹猴静脉输注8个周期S037 10 mg/kg组动物可见外周血单核细胞计数及百分比(#MONO 及%MONO)、IgG升高,胸腺淋巴细胞减少,脾脏红髓组织细胞有丝分裂象增多、坏死,胸骨骨髓造血细胞减少,以及骨髓细胞计数粒系升高、淋巴细胞降低趋势。结论:在本试验条件下,食蟹猴静脉输注8个周期S037 10 mg/kg组可见一定的免疫抑制作用。
关 键 词: 药理学;抗体偶联药物;免疫毒性;免疫抑制;食蟹猴
Title: Immunotoxicity study of antibody-drug conjugate S037
Author: LU Jing, LI Jianxiang, ZHANG Xuefeng
Organization: School of Public Health, Medical College of Soochow University; Jiangsu Tripod Preclinical Research Laboratories Co., Ltd.
Abstract: Objective: To observe the changes of general immunotoxicity related parameters after antibody-drug conjugate (ADC) S037 was administered to cynomolgus monkey via repeated intravenous infusion, providing scientific basis for safety evaluation. Methods: 40 cynomolgus monkeys of 3-5 years old were divided into 4 groups randomly, each group with 5 males and 5 females. The vehicle control group was given 0.9% sodium chloride injection. The S037 dosage of low, middle and high dose groups were 0.6, 2, 10 mg/kg, respectively. Intravenous infusion was administered for 8 cycles (once per 3 weeks as 1 administration cycle), and drug withdrawal to recover for 6 weeks. The immunotoxicity evaluation index included hematology (WBC and WBC classification percentages and counts), serum biochemistry (TP, ALB and A/G), immune organs of gross anatomy, organ weights (thymus and spleen), histopathology (thymus, spleen, submaxillary lymph nodes and mesenteric lymph nodes) and bone marrow smear, immune globin (IgG, IgA, IgM), complement (C3 and C4), circulating immune complex (CIC) and the lymphocytes groups. Results: Cynomolgus monkey was administered with intravenous infusion for 8 cycles, in S037 of 10 mg/kg group, #MONO, %MONO and IgG increased, thymus lymphocytes decreased, red pulp tissue cells mitosis increased in spleen, even necrosis, hematopoietic cells in the bone marrow of the sternum reduced, bone marrow cell granulosa count increased, and lymphocytes depleted. Conclusion: Under the conditions of this study, certain immune suppression was observed in S037 of 10 mg/kg group of the cynomolgus monkey by intravenous infusion.
Key words: pharmacology; antibody-drug conjugate (ADC); immunotoxicity; immune suppression; cynomolgus monkey
发表期数: 2018年12月第23期
引用格式: 鲁静,李建祥,张雪峰. 抗体偶联药物S037的免疫毒性研究[J]. 中国科技论文在线精品论文,2018,11(23):2375-2382.
 
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