双特异性抗体的结构设计及其装配工艺研究进展  

Structure design of bispecific antibodies and progress in the assembly process

作　　者：黎晓维 刘慧芳 王海彬 李锋 

机构地区：[1]北京天广实生物技术股份有限公司,北京101111 [2]浙江海正药业股份有限公司,台州318000

出　　处：《中国新药杂志》2014年第20期2430-2436,共7页Chinese Journal of New Drugs

摘　　要：双特异性抗体因其双靶向和可介导T细胞肿瘤杀伤的特点,被广泛应用于肿瘤和自身免疫性疾病的治疗。随着重组技术的进步,多种结构类型的双特异性抗体被开发出来,包括具有Fc结构域的类IgG(IgG-like)抗体以及小型化抗体。多种重组技术手段致力于解决轻重链随机错配的问题以及促进异源重链的二聚化。双特异性抗体的临床应用及商业化生产的关键点在于目标异源二聚体装配和纯化的可行性。体外装配和共培养策略具有更简单的工艺流程和更高的工艺可控性,可促进两种异源抗体的精确装配。Bispecific antibodies have the dual-targeting and T cell-mediated tumor cell killing properties,and therefore have been widely applied in the treatment of cancer and autoimmune diseases. Progress in antibody engineering technology had led to the development of various types of bispecific antibodies,including IgG-like bispecific antibodies and small bispecific antibodies. Multiple recombinant strategies have been used to resolve the mispairing problem between light and heavy chains,as well as to enforce the heterodimerization between correct heavy chains. The critical point of clinical application and commercial-scale manufacturing of bispecific antibodies is the amenability to assembly and purification of target heterodimers. The precision assembly of the heterodimers has been facilitated by in vitro assembly and co-culture strategies,which has the merits of simpler process scheme and higher process controllability.

关 键 词：双特异性抗体 异源二聚化 体外装配 杵臼结构 可控的Fab臂交换 共培养 

分 类 号：R915[医药卫生—微生物与生化药学]