6IAS

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

Summary for 6IAS

• Entry DOI: 10.2210/pdb6ias/pdb
• Descriptor: Fab NKp46-1 heavy chain, Fab NKp46-1 light chain (3 entities in total)
• Functional Keywords: therapeutic antibody, immune system
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 46478.77

Authors

Roussel, A.,Amigues, B. (deposition date: 2018-11-27, release date: 2019-06-12, Last modification date: 2019-06-26)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.75 Å)