6JJP

Crystal structure of Fab of a PD-1 monoclonal antibody MW11-h317 in complex with PD-1

6JJP の概要

• エントリーDOI: 10.2210/pdb6jjp/pdb
• 分子名称: Heavy chain of MW11-h317, light chain of MW11-h317, Programmed cell death protein 1, ... (6 entities in total)
• 機能のキーワード: pd-1, monoclonal antibody, cancer treatment, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 128895.25

構造登録者

Wang, M.,Wang, J.,Wang, R.,Jiao, S.,Wang, S.,Zhang, J.,Zhang, M. (登録日: 2019-02-26, 公開日: 2019-10-30, 最終更新日: 2024-11-06)

主引用文献

Wang, M.,Wang, J.,Wang, R.,Jiao, S.,Wang, S.,Zhang, J.,Zhang, M.
Identification of a monoclonal antibody that targets PD-1 in a manner requiring PD-1 Asn58 glycosylation.
Commun Biol, 2:392-392, 2019

PubMed Abstract: Programmed cell death 1 (PD-1) is inhibitory receptor and immune checkpoint protein. Blocking the interaction of PD-1 and its ligands PD-L1/ L2 is able to active T-cell-mediated antitumor response. Monoclonal antibody-based drugs targeting PD-1 pathway have exhibited great promise in cancer therapy. Here we show that MW11-h317, an anti-PD-1 monoclonal antibody, displays high affinity for PD-1 and blocks PD-1 interactions with PD-L1/L2. MW11-h317 can effectively induce T-cell-mediated immune response and inhibit tumor growth in mouse model. Crystal structure of PD-1/MW11-h317 Fab complex reveals that both the loops and glycosylation of PD-1 are involved in recognition and binding, in which Asn58 glycosylation plays a critical role. The unique glycan epitope in PD-1 to MW11-h317 is different from the first two approved clinical PD-1 antibodies, nivolumab and pembrolizumab. These results suggest MW11-h317 as a therapeutic monoclonal antibody of PD-1 glycosylation-targeting which may become efficient alternative for cancer therapy.

PubMed: 31667366
DOI: 10.1038/s42003-019-0642-9

実験手法

X-RAY DIFFRACTION (2.9 Å)