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Antiviral Res. 2017 Feb 28. pii: S0166-3542(16)30618-0. doi: 10.1016/j.antiviral.2017.02.016. [Epub ahead of print]
Bispecific T-Cell engaging antibody constructs targeting a universally conserved part of the viral M2 ectodomain cure and prevent influenza A virus infection.
Pendzialek J1, Roose K2, Smet A2, Schepens B2, Kufer P1, Raum T1, Baeuerle PA1, Muenz M1, Saelens X2, Fiers W3.
Author information
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.
Copyright ? 2017. Published by Elsevier B.V.
KEYWORDS:
Antiviral; Bispecific T cell engaging antibody constructs; Influenza virus; M2 ectodomain
PMID: 28257797 DOI: 10.1016/j.antiviral.2017.02.016
[PubMed - as supplied by publisher]
Bispecific T-Cell engaging antibody constructs targeting a universally conserved part of the viral M2 ectodomain cure and prevent influenza A virus infection.
Pendzialek J1, Roose K2, Smet A2, Schepens B2, Kufer P1, Raum T1, Baeuerle PA1, Muenz M1, Saelens X2, Fiers W3.
Author information
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.
Copyright ? 2017. Published by Elsevier B.V.
KEYWORDS:
Antiviral; Bispecific T cell engaging antibody constructs; Influenza virus; M2 ectodomain
PMID: 28257797 DOI: 10.1016/j.antiviral.2017.02.016
[PubMed - as supplied by publisher]