Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein.

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Etat: Public
Version: de l'auteur
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Télécharger: 18790793_Postprint.pdf (8298.39 [Ko])
Etat: Public
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ID Serval
serval:BIB_3BD43C71B7A9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein.
Périodique
Protein engineering, design and selection
Auteur(s)
Germain C., Campigna E., Salhi I., Morisseau S., Navarro-Teulon I., Mach J.P., Pèlegrin A., Robert B.
ISSN
1741-0134
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
21
Numéro
11
Pages
665-672
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Natural killer (NK) cells are at the crossroad between innate and adaptive immunity and play a major role in cancer immunosurveillance. NK cell stimulation depends on a balance between inhibitory and activating receptors, such as the stimulatory lectin-like receptor NKG2D. To redirect NK cells against tumor cells, we designed bifunctional proteins able to specifically bind tumor cells and to induce their lysis by NK cells, after NKG2D engagement. To this aim, we used the 'knob into hole' heterodimerization strategy, in which 'knob' and 'hole' variants were generated by directed mutagenesis within the CH3 domain of human IgG1 Fc fragments fused to an anti-CEA or anti-HER2 scFv or to the H60 murine ligand of NKG2D, respectively. We demonstrated the capacity of the bifunctional proteins produced to specifically coat tumor cells surface with H60 ligand. Most importantly, we demonstrated that these bifunctional proteins were able to induce an NKG2D-dependent and antibody-specific tumor cell lysis by murine NK cells. Overall, the results show the possibility to redirect NK cytotoxicity to tumor cells by a new format of recombinant bispecific antibody, opening the way of potential NK cell-based cancer immunotherapies by specific activation of the NKG2D receptor at the tumor site.
Mots-clé
Animals, Blotting, Western, Cell Death/immunology, Cell Line, Tumor, Cytotoxicity, Immunologic, Electrophoresis, Gel, Two-Dimensional, Humans, Intercellular Signaling Peptides and Proteins/immunology, Killer Cells, Lymphokine-Activated/immunology, Killer Cells, Natural/immunology, Killer Cells, Natural/metabolism, Mice, Minor Histocompatibility Antigens/immunology, Recombinant Proteins/immunology, Tumor Cells, Cultured/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/11/2009 10:21
Dernière modification de la notice
20/08/2019 14:31
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