Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy
Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy
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用于癌症免疫治疗的 D 肽拮抗剂阻断 PD-1/PD-L1 相互作用。
DOI：
10.1002/anie.201506225
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发表时间：
2015-09-28
影响因子：
16.6
通讯作者：
Gao, Yan-Feng
中科院分区：
文献类型：
--
作者：
Chang, Hao-Nan;Liu, Bei-Yuan;Gao, Yan-Feng
阻断跨膜蛋白程序性细胞死亡蛋白 1 (PD-1) 及其配体 PD-L1 之间的蛋白质-蛋白质相互作用已成为治疗癌症的一种有前途的免疫疗法。利用镜像噬菌体展示技术，我们开发了第一个针对PD-1/PD-L1通路的抗水解D肽拮抗剂。优化后的化合物(D) PPA-1在体外能够以0.51 μM的亲和力与PD-L1结合。细胞水平的阻断试验和荷瘤小鼠实验表明，(D) PPA-1 还可以有效破坏体内 PD-1/PD-L1 相互作用。因此，D-肽拮抗剂可能为癌症免疫治疗提供新型的低分子量候选药物。
Blockade of the protein-protein interaction between the transmembrane protein programmed cell death protein 1 (PD-1) and its ligand PD-L1 has emerged as a promising immunotherapy for treating cancers. Using the technology of mirror-image phage display, we developed the first hydrolysis-resistant D-peptide antagonists to target the PD-1/PD-L1 pathway. The optimized compound (D) PPA-1 could bind PD-L1 at an affinity of 0.51 μM in vitro. A blockade assay at the cellular level and tumor-bearing mice experiments indicated that (D) PPA-1 could also effectively disrupt the PD-1/PD-L1 interaction in vivo. Thus D-peptide antagonists may provide novel low-molecular-weight drug candidates for cancer immunotherapy.