再循环抗体的研究进展

Advance in research on recycling antibody

摘要:

单克隆抗体因其与抗原结合具有高度特异性与强亲和力，已成为抗体药物研发的主要类型。但随着天然单克隆抗体的深入研究，它的诸多缺陷也浮出水面，如与抗原结合次数有限、带来非预期的抗体清除效应和抗原累积效应。人们不再局限于天然抗体的筛选，而是想通过改造提升抗体药物的药效。近年来，一类新型再循环抗体的问世，很好地解决了天然单克隆抗体发展的瓶颈。再循环抗体可以在胞外结合抗原，在细胞内与抗原解离，使抗体结合抗原次数最大化，减少抗原介导的抗体清除效应和抗体介导的抗原累积效应，并且再循环抗体可以通过进一步的Fc改造来加强与Fc受体的亲和力。文中综述了再循环抗体的研究进展，包括其特点、改造方法及展望。

Abstract:

Monoclonal antibodies have become the main type of antibody drug because of their high specificity and strong affinity to antigen. However, with the intensive study of the natural monoclonal antibody, many defects have faced, such as the limit times of binding to antigen, the unanticipated antibody clearance and antigen accumulation. Therefore, studies are no longer limited to the natural antibody screening, but rather to improve the efficiency of antibody drugs by engineering. In recent years, the bottlenecks in the development of conventional antibody have been solved effectively since the discovery of a novel recycling antibody. Recycling antibody binds to an antigen in plasma and dissociates from the antigen in endosome, thus maximizing the use of antibody and reducing antigen-mediated antibody clearance and antibody-mediated antigen accumulation. In addition, recycling antibodies can enhance the affinity with Fc receptors through further Fc modification. This paper reviews the research progress of circulating antibodies, including its characteristics, transformation methods and prospects.