Bispecific T-Cell engaging antibody constructs targeting a universally conserved part of the viral M2 ectodomain cure and prevent influenza A virus infection.

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Bispecific T-Cell engaging antibody constructs targeting a universally conserved part of the viral M2 ectodomain cure and prevent influenza A virus infection.

Antiviral Res. 2017 Feb 28;:

Authors: Pendzialek J, Roose K, Smet A, Schepens B, Kufer P, Raum T, Baeuerle PA, Muenz M, Saelens X, Fiers W

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.

PMID: 28257797 [PubMed - as supplied by publisher]

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