6IAP
structure of human NKp46 in complex with antibody NKp46-1 and NKp46-4
Summary for 6IAP
| Entry DOI | 10.2210/pdb6iap/pdb |
| Descriptor | Natural cytotoxicity triggering receptor 1, Fab NKp46-4 light chain, Fab NKp46-4 heavy chain, ... (6 entities in total) |
| Functional Keywords | therapeutic antibody, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 113726.20 |
| Authors | Roussel, A.,Amigues, B. (deposition date: 2018-11-27, release date: 2019-06-12, Last modification date: 2024-10-16) |
| 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 Cited by 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: 31155232DOI: 10.1016/j.cell.2019.04.041 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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