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dc.contributor.author
Mufarrege, Eduardo Federico
dc.contributor.author
Haile, Lydia A.
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Echeverrigaray, Marina
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Verthelyi, Daniela
dc.date.available
2020-05-08T12:54:03Z
dc.date.issued
2019
dc.identifier.citation
Mufarrege, Eduardo Federico; Haile, Lydia A.; Echeverrigaray, Marina; Verthelyi, Daniela; Multiplexed Gene Expression as a Characterization of Bioactivity for Interferon Beta (IFN-β) Biosimilar Candidates: Impact of Innate Immune Response Modulating Impurities (IIRMIs); Springer; Aaps Journal; 21; 26; 2019; 1-11
dc.identifier.issn
1550-7416
dc.identifier.uri
http://hdl.handle.net/11336/104583
dc.description.abstract
Recombinant human interferon-β (rhIFN-β) therapy is the first-line treatment in relapsing-remitting forms of multiple sclerosis (MS). The mechanism of action underlying its therapeutic activity is only partially understood as IFN-βs induce the expression of over 1000 genes modifying multiple immune pathways. Currently, assessment of potency for IFN-β products is based on their antiviral effect, which is not linked to its therapeutic effect. Here, we explore the use of a multiplexed gene expression system to more broadly characterize IFN-β bioactivity. We find that MM6 cells stimulated with US-licensed rhIFN-βs induce a dose-dependent and reproducible pattern of gene expression. This pattern of gene expression was used to compare the bioactivity profile of biosimilar candidates with the corresponding US-licensed rhIFN-β products, Rebif and Betaseron. While the biosimilar candidate for Rebif matched the pattern of gene expression, there were differences in the expression of a subset of interferon-inducible genes including CXCL-10, CXCL-11, and GBP1 induced by the biosimilar candidate for Betaseron. Assessment of product impurities in both products suggested that the difference was rooted in the presence of innate immune response modulating impurities (IIRMIs) in the licensed product. These studies indicate that determining the expression levels for an array of reporter genes that monitor different pathways can be informative as part of the demonstration of biosimilarity or comparability for complex immunomodulatory products such as IFN-β, but the sensitivity of each gene to potential impurities in the product should be examined to fully understand the results.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
BIOACTIVITY
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BIOSIMILARITY
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COMPARABILITY
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GENE EXPRESSION
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IMPURITIES
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INNATE IMMUNE
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RESPONSE MODULATING IMPURITIES
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INTERFERON BETA
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Biotecnología relacionada con la Salud
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Biotecnología de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Multiplexed Gene Expression as a Characterization of Bioactivity for Interferon Beta (IFN-β) Biosimilar Candidates: Impact of Innate Immune Response Modulating Impurities (IIRMIs)
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-05-04T20:55:34Z
dc.journal.volume
21
dc.journal.number
26
dc.journal.pagination
1-11
dc.journal.pais
Alemania
dc.description.fil
Fil: Mufarrege, Eduardo Federico. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina
dc.description.fil
Fil: Haile, Lydia A.. Food And Drug Administration;
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Fil: Echeverrigaray, Marina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina
dc.description.fil
Fil: Verthelyi, Daniela. Universidad Nacional del Litoral; Argentina
dc.journal.title
Aaps Journal
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1208/s12248-019-0300-7
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