6IAP

structure of human NKp46 in complex with antibody NKp46-1 and NKp46-4

6IAP の概要

• エントリーDOI: 10.2210/pdb6iap/pdb
• 分子名称: Natural cytotoxicity triggering receptor 1, Fab NKp46-4 light chain, Fab NKp46-4 heavy chain, ... (6 entities in total)
• 機能のキーワード: therapeutic antibody, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 113726.20

構造登録者

Roussel, A.,Amigues, B. (登録日: 2018-11-27, 公開日: 2019-06-12, 最終更新日: 2024-10-16)

主引用文献

Gauthier, L.,Morel, A.,Anceriz, N.,Rossi, B.,Blanchard-Alvarez, A.,Grondin, G.,Trichard, S.,Cesari, C.,Sapet, M.,Bosco, F.,Rispaud-Blanc, H.,Guillot, F.,Cornen, S.,Roussel, A.,Amigues, B.,Habif, G.,Caraguel, F.,Arrufat, S.,Remark, R.,Romagne, F.,Morel, Y.,Narni-Mancinelli, E.,Vivier, E.
Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity.
Cell, 177:1701-1713.e16, 2019

PubMed Abstract: Over the last decade, various new therapies have been developed to promote anti-tumor immunity. Despite interesting clinical results in hematological malignancies, the development of bispecific killer-cell-engager antibody formats directed against tumor cells and stimulating anti-tumor T cell immunity has proved challenging, mostly due to toxicity problems. We report here the generation of trifunctional natural killer (NK) cell engagers (NKCEs), targeting two activating receptors, NKp46 and CD16, on NK cells and a tumor antigen on cancer cells. Trifunctional NKCEs were more potent in vitro than clinical therapeutic antibodies targeting the same tumor antigen. They had similar in vivo pharmacokinetics to full IgG antibodies and no off-target effects and efficiently controlled tumor growth in mouse models of solid and invasive tumors. Trifunctional NKCEs thus constitute a new generation of molecules for fighting cancer. VIDEO ABSTRACT.

PubMed: 31155232
DOI: 10.1016/j.cell.2019.04.041

実験手法

X-RAY DIFFRACTION (2.9 Å)