T细胞依赖的双特异性抗体结构设计的研究进展

Advances in structural design of T cell-dependent bispecific antibodies

随着抗体工程的不断发展,靶向CD3的T细胞依赖的双特异性抗体已经发展出多种多样的结构,从而满足更多临床治疗的需求。依据是否含有Fc段可将T细胞依赖的双特异性抗体分为IgG样和非IgG样两种结构。其中轻重链错配问题是双特异性抗体最常见的制备难点,为解决该问题,目前已有多种技术应用于其结构设计中,包括杵臼技术、结构域交换技术等。由于T细胞依赖的双特异性抗体的作用机制是将T细胞重定向至肿瘤细胞继而发挥杀伤作用,因此Fc段杀伤功能的沉默、靶点的亲和力设计,以及免疫突触形成的距离设计均是T细胞依赖的双特异性抗体结构设计的重点。本文将围绕以上针对T细胞依赖的双特异性抗体结构设计的研究进展进行总结。

With the development of antibody engineering,a diverse range of structures for T cell-dependent bispecific antibodies targeting CD3 have been devised to meet the needs of various clinical therapies.T cell-dependent bispecific antibodies can be categorized into IgG-like and non-IgG-like formats based on the presence or absence of an Fc domain.The most common difficulty in manufacturing bispecific antibodies is the mispairing between light and heavy chains.To overcome this challenge,several techniques,such as knob-into-hole and CrossMab technologies,have been implemented for structural design.Given that the mechanism of action of T cell-dependent bispecific antibodies is to redirect T cells to tumor cells to induce a killing effect,abolishment of Fc domain effector function,the affinity design of the target,and the distance design of immune synapse formation are all focal points in the structural design of T cell-dependent bispecific antibodies.This review aims to provide an overview of recent advances in the structural design of T cell-dependent bispecific antibodies.