重组方法制备象IgG的双特异性抗体

Recombinant Approaches to IgG-like Bispecific Antibodies

用传统的方法,象杂交瘤技术和化学合成方法,制备高质量高产量的双特异性单克隆抗体(BsAb,bispecific antibodies),现在还存在着很多问题。虽然重组BsAb片段(例如双特异抗体和串联单链Fv)快速而显著的发展,但是全长象IgG BsAb的成功设计和制备还受到限制。不像小片段,在血清中,象IgG BsAb有很长的半衰期并能支持二次免疫功能,依赖抗体的细胞毒性和补体介导的细胞毒性。作为治疗试剂象IgG BsAb的发展,要以设计重组BsAb结构(或者形式)和高效的产量为重要的基础。这篇文章主要围绕着各种基因工程的重组方法进展以及制备象IgG BsAb来阐述的。

One of the major obstacles in the development ofbispecific antibodies（BsAb） has been the difficulty of producing the materials in sufficient quality and quantity by traditional technologies,such as the hybrid hybridoma and chemical conjugation methods. In constrast to the rapid and significant progress in the development of recombinant BsAb fragments（such as diabody and tandem single chain Fv）, the successful design and production of full length IgG-like BsAb has been limited. Compared to smaller fragments, IgG-like BsAb has long serum half-life and capable of supporting secondary immune fuction, such as antibody-denpendent celluar cytotoxicity and complement-mediated cytotoxicity. The development of IgG-like BsAb as therapeutic agents will heavily on research progress in the design of recombinant BsAb constructs（or formats） and production efficiency. This review will focus on recent advances in various recombinant approaches to the engineering and production of IgG-like BsAb.