摘要
抗体偶联药物(Antibody Drug Conjugate,ADC),是通过连接子将高细胞毒性化合物连接到靶向肿瘤抗原的抗体上,利用抗体靶向识别将化合物递呈至肿瘤细胞表面,杀死肿瘤细胞。ADC药物同时具有抗体和化学药物属性,是将两者的优势结合,极大地提高了药物安全有效性。ADC药物结构复杂,在抗原识别表位、连接位点、连接子以及小分子药物各组分均存在特异性,所以在开展安全性评价研究时有一定的特殊性。本文将从动物种属选择、一般毒性研究、毒代动力学研究、组织交叉反应、免疫原性检测、安全药理研究、遗传毒性研究等方面,阐述ADC药物临床前安全性评价的考虑要点和研究策略。
Antibody drug conjugate（ADC） is produced by coupling high cytotoxic chemical with monoclonal antibody（mAb） through a linker. By being conjugated with antibody targeting to the tumor antigen, the chemical is delivered to the surface of tumor cells, and kills the tumor cells. ADCs possess the properties and advantages of both monoclonal antibodies and chemical drugs, and their safety and effectiveness are improved greatly. Due to the complex structure, specificities in antigen recognition epitopes, linking sites, linkers, and small molecular chemicals, the safety evaluation studies of ADCs have some special considerations. In this paper, the main considerations and research strategies of preclinical safety evaluation of ADCs are introduced from the following aspects, including animal species selection, general toxicity study, toxicokinetic study, tissue cross reaction, immunogenicity test, safety pharmacology, genotoxicity study, and so on.
作者
王欣
耿兴超
刘丽
文海若
霍艳
Wang Xin;Geng Xingchao;Liu Li;Wen Hairuo;Huo Yan(National Institutes for Food and Drug Control,Beijing Key Lab for Pre-clinical Safety Evaluation of Drugs,Beijing 100176,China)
出处
《中国药事》
CAS
2018年第11期1515-1519,共5页
Chinese Pharmaceutical Affairs
基金
十二五国家科技重大专项“生物大分子药物特殊评价关键技术研究”(编号2015ZX09501007-004)
