免疫检查点
PD-L1
单克隆抗体
抗体
细胞生物学
癌症免疫疗法
小分子
生物
化学
受体
计算生物学
免疫系统
免疫疗法
生物化学
免疫学
作者
Krzysztof Żak,P. Grudnik,Katarzyna Magiera,Alexander Dömlingꝉ,Grzegorz Dubin,Tad A. Holak
出处
期刊:Structure
[Elsevier]
日期:2017-08-01
卷期号:25 (8): 1163-1174
被引量:247
标识
DOI:10.1016/j.str.2017.06.011
摘要
Cancer cells can avoid and suppress immune responses through activation of inhibitory immune checkpoint proteins, such as PD-1, PD-L1, and CTLA-4. Blocking the activities of these proteins with monoclonal antibodies, and thus restoring T cell function, has delivered breakthrough therapies against cancer. In this review, we describe the latest work on structural characterization of the checkpoint proteins, their interactions with cognate ligands and with therapeutic antibodies. Structures of the extracellular portions of these proteins reveal that they all have a similar modular structure, composed of small domains similar in topology to the domains found in antibodies. Structural basis for blocking the PD-1/PD-L1 interaction by small molecules is illustrated with the compound BMS-202 that binds to and induces dimerization of PD-L1.
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