双特异性抗体副产物去除策略

Insight into the Purification Strategies for Removing the Byproducts of Bispecific Antibodies

双特异性抗体是一种可以同时结合两种靶点的抗体,与单特异性抗体相比具有疗效高、毒副作用小的优点,因此成为近年来的研究热点。但双特异性抗体是由两种不同的重链和轻链所组成,而且重、轻链的表达难以控制在同一水平,因此在双特异性抗体的组装过程中极易出现各种错配副产物,大大增加了下游纯化的难度与成本。近年来,多家制药公司研发出商业化的双特异性抗体制备平台,这些平台利用独特的分子设计策略极大提升了双特异性抗体的组装成功率。然而,各种双抗分子设计策略不足以完全避免副产物的产生,因此还需要配合各种层析方式来进一步去除双抗分子副产物以提升产品质量。综述了近年来几种主流双特异性抗体研发设计平台,系统归纳了用于去除同源二聚体、半抗体、3/4抗体及聚集体的层析方法,以期为双特异性抗体纯化提供理论依据。

Bispecific antibodies can simultaneously bind to two targets.Compared with monospecific antibodies,they have the advantages of high efficacy and less toxic and side effects,so they have become a research hotspot in recent years.However,since bispecific antibodies are composed of different heavy chains and light chains,and the expression of heavy and light chains is difficult to control at the same level,it is very easy to form by-products,which greatly increase the difficulty and cost of downstream purification.In recent years,several pharmaceutical companies have developed bispecific antibody preparation platforms,which have greatly improved the success rate of bispecific antibody assembly.However,various double-antibody molecular design strategies are not enough to completely prevent the production of by-products,so various chromatographic methods are needed to further remove the by-products of double-antibody molecules to improve product quality.This paper reviews several mainstream bispecific antibody design platforms in recent years,and systematically summarizes the chromatographic methods for removing homodimers,half antibodies and 3/4 antibodies and aggregates.The comprehensive information should be helpful to provide a theoretical basis for bispecific antibody purification.