6iap

From Proteopedia

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

PDB ID 6iap

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Structural highlights

6iap is a 5 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NCTR1_HUMAN Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.^[1]

Publication Abstract from PubMed

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.

Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity.,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 Cell. 2019 May 30. pii: S0092-8674(19)30460-X. doi: 10.1016/j.cell.2019.04.041. PMID:31155232^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L, Moretta L, Biassoni R, Moretta A. Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity. J Exp Med. 1998 Sep 7;188(5):953-60. PMID:9730896
↑ 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. 2019 May 30. pii: S0092-8674(19)30460-X. doi: 10.1016/j.cell.2019.04.041. PMID:31155232 doi:http://dx.doi.org/10.1016/j.cell.2019.04.041