title: Bispecific T cell engaging antibody constructs targeting a universally conserved part of the viral M2 ectodomain cure and prevent influenza A virus infection.
abstract: The ectodomain of the influenza A matrix protein 2 (M2e) is highly conserved amongst all influenza virus A subtypes. M2e is present on the surface of influenza A virus-infected cells, and therefore a suitable target for broadly protective therapies. We designed bispecific T cell engaging (BiTE®) antibody constructs specific for M2e by genetically fusing a single chain variable fragment (scFv) derived from an M2e-specific murine monoclonal antibody with a CD3ɛ-specific scFv. These so-called FLU BiTE®antibody constructs selectively mediate T cell dependent lysis of M2-expressing and influenza A virus infected cells and protect BALB/c mice against challenge with different influenza A virus subtypes. By humanizing the M2e-binding scFv, we generated human-like FLU BiTE®antibody constructs, with increased in vitro cytotoxic activity and in vivo protective capacity against influenza A virus infection. FLU BiTE®antibody constructs represent a promising new curative and prophylactic treatment option for influenza disease.
authors.affiliation: ARM, Amgen Research (Munich) GmbH, Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Pendzialek
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium.
authors.forename: Kenny
authors.initials: K
authors.lastname: Roose
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium.
authors.forename: Anouk
authors.initials: A
authors.lastname: Smet
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium.
authors.forename: Bert
authors.initials: B
authors.lastname: Schepens
authors.affiliation: ARM, Amgen Research (Munich) GmbH, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kufer
authors.affiliation: ARM, Amgen Research (Munich) GmbH, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Raum
authors.affiliation: ARM, Amgen Research (Munich) GmbH, Munich, Germany.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Baeuerle
authors.affiliation: ARM, Amgen Research (Munich) GmbH, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Muenz
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium. Electronic address: walter.fiers@skynet.be.
authors.forename: Walter
authors.initials: W
authors.lastname: Fiers
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D003601:Cytotoxicity Tests, Immunologic; D007156:Immunologic Memory; D009980:Influenza A virus / Q000737:chemistry* / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Antiviral; Bispecific T cell engaging antibody constructs; Influenza virus; M2 ectodomain