6HIG

hPD-1/NBO1a Fab complex

6HIG の概要

• エントリーDOI: 10.2210/pdb6hig/pdb
• 分子名称: Heavy Chain, Light Chain, Programmed cell death protein 1, ... (4 entities in total)
• 機能のキーワード: non-blocking antibody, pd-1/pd-l1 pathway, anti-pd-1 antibody, tumor clearance, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 61731.74

構造登録者

Loredo-Varela, J.L.,Fenwick, C.,Pantaleo, G.,Weissenhorn, W. (登録日: 2018-08-29, 公開日: 2019-06-05, 最終更新日: 2024-10-23)

主引用文献

Fenwick, C.,Loredo-Varela, J.L.,Joo, V.,Pellaton, C.,Farina, A.,Rajah, N.,Esteves-Leuenberger, L.,Decaillon, T.,Suffiotti, M.,Noto, A.,Ohmiti, K.,Gottardo, R.,Weissenhorn, W.,Pantaleo, G.
Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway.
J.Exp.Med., 216:1525-1541, 2019

PubMed Abstract: Classical antagonistic antibodies (Abs) targeting PD-1, such as pembrolizumab and nivolumab, act through blockade of the PD-1-PDL-1 interaction. Here, we have identified novel antagonistic anti-PD-1 Abs not blocking the PD-1-PDL-1 interaction. The nonblocking Abs recognize epitopes on PD-1 located on the opposing face of the PDL-1 interaction and overlap with a newly identified evolutionarily conserved patch. These nonblocking Abs act predominantly through the CD28 coreceptor. Importantly, a combination of blocking and nonblocking Abs synergize in the functional recovery of antigen-specific exhausted CD8 T cells. Interestingly, nonblocking anti-PD-1 Abs have equivalent antitumor activity compared with blocker Abs in two mouse tumor models, and combination therapy using both classes of Abs enhanced tumor suppression in the mouse immunogenic tumor model. The identification of the novel nonblocker anti-PD-1 Abs and their synergy with classical blocker Abs may be instrumental in potentiating immunotherapy strategies and antitumor activity.

PubMed: 31123083
DOI: 10.1084/jem.20182359

実験手法

X-RAY DIFFRACTION (2.2 Å)