文献类型：期刊文献

英文题名：Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1

作者：Jiang, Mengzhen[1];Liu, Man[1];Liu, Guodi[1];Ma, Jiawen[1];Zhang, Lixin[1];Wang, Shenlin[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2023

卷号：15

期号：1

外文期刊名：MABS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001041355400001)】；

基金：S.W was supported by the National Natural Science Foundation of China (grant numbers 22274050) and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Antibody structure; antibody-antigen interactions; PD-1

摘要：Antibody-based immune checkpoint blockade (ICB)-based therapeutics have become effective clinical applications for cancers. Applications of monoclonal antibodies (mAbs) to de-activate the PD-1-PD-L1 pathway could effectively reverse the phenotype of depleted activated thymocytes (T cells) to recover their anti-tumoral activities. High-resolution structures of the complexes of the therapeutic monoclonal antibodies with PD-1 or PD-L1 have revealed the key inter-molecular interactions and provided valuable insights into the fundamental mechanisms by which these antibodies inhibit PD-L1-PD-1 binding. Each anti-PD-1 mAb exhibits a unique blockade mechanism, such as interference with large PD-1-PD-L1 contacting interfaces, steric hindrance by overlapping a small area of this site, or binding to an N-glycosylated site. In contrast, all therapeutic anti-PD-L1 mAbs bind to a similar area of PD-L1. Here, we summarized advances in the structural characterization of the complexes of commercial mAbs that target PD-1 or PD-L1. In particular, we focus on the unique characteristics of those mAb structures, epitopes, and blockade mechanisms. It is well known that the use of antibodies as anti-tumor drugs has increased recently and both PD-1 and PD-L1 have attracted substantial attention as target for antibodies derived from new technologies. By focusing on structural characterization, this review aims to aid the development of novel antibodies targeting PD-1 or PD-L1 in the future.