[关键词]
[摘要]
抗体偶联药物、双特异性抗体等新型抗体已成为近年来抗体工程领域的研究热点,由于其具有特异性高、选择性强和非细胞毒性等优点,在肿瘤治疗领域中具有广阔的应用前景。但该类药物结构和功能相对复杂,给安全性带来特殊风险。在临床前安全性评价中,需要根据其特点和可能介导的毒性作用机制,建立科学的评价方案。通过对新型抗体类药物的类型、结构特点、作用方式以及主要的毒性风险进行综述,并结合已批准的新型抗体类药物的非临床安全性评价实例,探索新型抗体类药物的临床前安全性评价策略。
[Key word]
[Abstract]
Antibody drug conjugates (ADCs) and Bispecific Antibodies are emerging as the promising class of new biopharmaceutical which have become a research focus in antibody engineering. Due to its specificity and less adverse effect,these new antibody drugs have a wide application future in cancer immunotherapy. From the nonclinical safety perspective, ADCs and Bispecific Antibodies present unique challenges to standard toxicology testing due to the complex components and mechanism of action. The impact of these biochemical differences on the safety must be considered when determining the types of nonclinical safety studies. The aim of this article is to review the unique characteristic, mode of action, determinants of toxicity, and preclinical studies of ADCs and Bispecific Antibodies to discuss how recent advances in our understanding of drug-mediated toxicity can be used to guide the types of preclinical safety studies.
[中图分类号]
[基金项目]
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”(2015ZX09501007-004);中国食品药品检定研究院中青年发展研究基金(2014C5)