Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis

Autores
Sterin Prync, Aída Edith; Yankilevich, Patricio; Barrero, Paola Roxana; Bello, R.; Marangunich, L.; Vidal, A.; Criscuolo, M.; Benasayag, L.; Famulari, A. L.; Domínguez, R. O.; Kauffman, Marcelo Andres; Diez, Roberto Alejandro
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: Recombinant human interferon-beta (IFN-b) is a well-established treatment for multiple sclerosis (MS). The regulatory process for marketing authorization of biosimilars is currently under debate in certain countries. In the EU, EMEA has clearly defined the process including overarching and product-specific guidelines, which includes clinical testing. Biosimilarity needs to be based on comparability criteria, including at least molecular characterization, biological activity relevant for the therapeutic effect and relative bioavailability (“bioequivalence”). In the case of such complex diseases as MS, where the effect of treatment is not so directly measurable, in vitro tools can provide additional data to support comparability. Genomic microarrays assays might be useful to compare multisource biopharmaceuticals. The aim of the present study was to compare the pharmacodynamic genomic effects (in terms of transcriptional regulation) of two recombinant human IFN-β1a preparations on lymphocytes of multiple sclerosis patients using a whole genome microarray assay. Methods: We performed an ex vivo whole genome expression profiling of the effect of two preparations of IFN-β1a on non-adherent mononuclears from five relapsing-remitting MS patients analyzing microarrays (CodeLink™ Human Whole Genome). Patients blood was drawn, PBMCs isolated and cultured in three different conditions: culture medium (control), 1,000 U/ml of IFN-β1a (BLA- (STOFERON™, Bio Sidus) and 1,000 U/ml of IFN-β1a (REBIF™, Serono) RNA was purified from non-adherent cells (mostly lymphocytes), amplified and hybridized. Raw data were generated by CodeLink™ proprietary software. Data normalization, quality control and analysis of differential gene expression between treatments were done using linear model for microarray data. Functional annotation analysis of IFN-β1a MS treatment transcription was done using DAVID. Results: Out of the approximately 45,000 human sequences examined, no evidence of differential regulation was found when both treatments were compared (minimum adjusted p-value > 0.999). The IFN-β1a effect differentially regulated the expression of 868 genes. The expression of standard markers such as GTP cyclohidrolase, MxA, and OAS isoenzymes A and B changed as a consequence of the action of IFN-β1a. Conclusions: This exhaustive and highly sensitive assay did not show differences in the genomic expression profile of these two products under the assayed experimental conditions. These results suggest that this technology might be useful for the initial comparison of biosimilars, being part of a comprehensive comparability program that includes clinical testing.
Fil: Sterin Prync, Aída Edith. Bio Sidus S.A.; Argentina
Fil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Bio Sidus S.A.; Argentina
Fil: Barrero, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Bello, R.. Bio Sidus S.A.; Argentina
Fil: Marangunich, L.. Bio Sidus S.A.; Argentina
Fil: Vidal, A.. Bio Sidus S.A.; Argentina
Fil: Criscuolo, M.. Bio Sidus S.A.; Argentina
Fil: Benasayag, L.. Centro Neurológico Integral ; Argentina
Fil: Famulari, A. L.. Fundación Argentina contra las Enfermedades Neurológicas del Envejecimiento; Argentina
Fil: Domínguez, R. O.. Fundación Argentina contra las Enfermedades Neurológicas del Envejecimiento; Argentina
Fil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Bio Sidus S.A.; Argentina
Fil: Diez, Roberto Alejandro. Bio Sidus S.A.; Argentina
Materia
BIOSIMILARS
INTERFERON-BETA
LYMPHOCYTES
MICROARRAYS
MULTIPLE SCLEROSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/137187

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysisSterin Prync, Aída EdithYankilevich, PatricioBarrero, Paola RoxanaBello, R.Marangunich, L.Vidal, A.Criscuolo, M.Benasayag, L.Famulari, A. L.Domínguez, R. O.Kauffman, Marcelo AndresDiez, Roberto AlejandroBIOSIMILARSINTERFERON-BETALYMPHOCYTESMICROARRAYSMULTIPLE SCLEROSIShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objectives: Recombinant human interferon-beta (IFN-b) is a well-established treatment for multiple sclerosis (MS). The regulatory process for marketing authorization of biosimilars is currently under debate in certain countries. In the EU, EMEA has clearly defined the process including overarching and product-specific guidelines, which includes clinical testing. Biosimilarity needs to be based on comparability criteria, including at least molecular characterization, biological activity relevant for the therapeutic effect and relative bioavailability (“bioequivalence”). In the case of such complex diseases as MS, where the effect of treatment is not so directly measurable, in vitro tools can provide additional data to support comparability. Genomic microarrays assays might be useful to compare multisource biopharmaceuticals. The aim of the present study was to compare the pharmacodynamic genomic effects (in terms of transcriptional regulation) of two recombinant human IFN-β1a preparations on lymphocytes of multiple sclerosis patients using a whole genome microarray assay. Methods: We performed an ex vivo whole genome expression profiling of the effect of two preparations of IFN-β1a on non-adherent mononuclears from five relapsing-remitting MS patients analyzing microarrays (CodeLink™ Human Whole Genome). Patients blood was drawn, PBMCs isolated and cultured in three different conditions: culture medium (control), 1,000 U/ml of IFN-β1a (BLA- (STOFERON™, Bio Sidus) and 1,000 U/ml of IFN-β1a (REBIF™, Serono) RNA was purified from non-adherent cells (mostly lymphocytes), amplified and hybridized. Raw data were generated by CodeLink™ proprietary software. Data normalization, quality control and analysis of differential gene expression between treatments were done using linear model for microarray data. Functional annotation analysis of IFN-β1a MS treatment transcription was done using DAVID. Results: Out of the approximately 45,000 human sequences examined, no evidence of differential regulation was found when both treatments were compared (minimum adjusted p-value > 0.999). The IFN-β1a effect differentially regulated the expression of 868 genes. The expression of standard markers such as GTP cyclohidrolase, MxA, and OAS isoenzymes A and B changed as a consequence of the action of IFN-β1a. Conclusions: This exhaustive and highly sensitive assay did not show differences in the genomic expression profile of these two products under the assayed experimental conditions. These results suggest that this technology might be useful for the initial comparison of biosimilars, being part of a comprehensive comparability program that includes clinical testing.Fil: Sterin Prync, Aída Edith. Bio Sidus S.A.; ArgentinaFil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Bio Sidus S.A.; ArgentinaFil: Barrero, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bello, R.. Bio Sidus S.A.; ArgentinaFil: Marangunich, L.. Bio Sidus S.A.; ArgentinaFil: Vidal, A.. Bio Sidus S.A.; ArgentinaFil: Criscuolo, M.. Bio Sidus S.A.; ArgentinaFil: Benasayag, L.. Centro Neurológico Integral ; ArgentinaFil: Famulari, A. L.. Fundación Argentina contra las Enfermedades Neurológicas del Envejecimiento; ArgentinaFil: Domínguez, R. O.. Fundación Argentina contra las Enfermedades Neurológicas del Envejecimiento; ArgentinaFil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Bio Sidus S.A.; ArgentinaFil: Diez, Roberto Alejandro. Bio Sidus S.A.; ArgentinaDustri-Verlag Dr. Karl Feistle2008-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/137187Sterin Prync, Aída Edith; Yankilevich, Patricio; Barrero, Paola Roxana; Bello, R.; Marangunich, L.; et al.; Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis; Dustri-Verlag Dr. Karl Feistle; International Journal of Clinical Pharmacology and Therapeutics; 46; 2; 2-2008; 64-710946-1965CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.dustri.com/article_response_page.html?artId=1673&doi=10.5414/CPP46064&L=0info:eu-repo/semantics/altIdentifier/doi/10.5414/cpp46064info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:13:06Zoai:ri.conicet.gov.ar:11336/137187instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:13:06.34CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
title Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
spellingShingle Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
Sterin Prync, Aída Edith
BIOSIMILARS
INTERFERON-BETA
LYMPHOCYTES
MICROARRAYS
MULTIPLE SCLEROSIS
title_short Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
title_full Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
title_fullStr Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
title_full_unstemmed Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
title_sort Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis
dc.creator.none.fl_str_mv Sterin Prync, Aída Edith
Yankilevich, Patricio
Barrero, Paola Roxana
Bello, R.
Marangunich, L.
Vidal, A.
Criscuolo, M.
Benasayag, L.
Famulari, A. L.
Domínguez, R. O.
Kauffman, Marcelo Andres
Diez, Roberto Alejandro
author Sterin Prync, Aída Edith
author_facet Sterin Prync, Aída Edith
Yankilevich, Patricio
Barrero, Paola Roxana
Bello, R.
Marangunich, L.
Vidal, A.
Criscuolo, M.
Benasayag, L.
Famulari, A. L.
Domínguez, R. O.
Kauffman, Marcelo Andres
Diez, Roberto Alejandro
author_role author
author2 Yankilevich, Patricio
Barrero, Paola Roxana
Bello, R.
Marangunich, L.
Vidal, A.
Criscuolo, M.
Benasayag, L.
Famulari, A. L.
Domínguez, R. O.
Kauffman, Marcelo Andres
Diez, Roberto Alejandro
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BIOSIMILARS
INTERFERON-BETA
LYMPHOCYTES
MICROARRAYS
MULTIPLE SCLEROSIS
topic BIOSIMILARS
INTERFERON-BETA
LYMPHOCYTES
MICROARRAYS
MULTIPLE SCLEROSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objectives: Recombinant human interferon-beta (IFN-b) is a well-established treatment for multiple sclerosis (MS). The regulatory process for marketing authorization of biosimilars is currently under debate in certain countries. In the EU, EMEA has clearly defined the process including overarching and product-specific guidelines, which includes clinical testing. Biosimilarity needs to be based on comparability criteria, including at least molecular characterization, biological activity relevant for the therapeutic effect and relative bioavailability (“bioequivalence”). In the case of such complex diseases as MS, where the effect of treatment is not so directly measurable, in vitro tools can provide additional data to support comparability. Genomic microarrays assays might be useful to compare multisource biopharmaceuticals. The aim of the present study was to compare the pharmacodynamic genomic effects (in terms of transcriptional regulation) of two recombinant human IFN-β1a preparations on lymphocytes of multiple sclerosis patients using a whole genome microarray assay. Methods: We performed an ex vivo whole genome expression profiling of the effect of two preparations of IFN-β1a on non-adherent mononuclears from five relapsing-remitting MS patients analyzing microarrays (CodeLink™ Human Whole Genome). Patients blood was drawn, PBMCs isolated and cultured in three different conditions: culture medium (control), 1,000 U/ml of IFN-β1a (BLA- (STOFERON™, Bio Sidus) and 1,000 U/ml of IFN-β1a (REBIF™, Serono) RNA was purified from non-adherent cells (mostly lymphocytes), amplified and hybridized. Raw data were generated by CodeLink™ proprietary software. Data normalization, quality control and analysis of differential gene expression between treatments were done using linear model for microarray data. Functional annotation analysis of IFN-β1a MS treatment transcription was done using DAVID. Results: Out of the approximately 45,000 human sequences examined, no evidence of differential regulation was found when both treatments were compared (minimum adjusted p-value > 0.999). The IFN-β1a effect differentially regulated the expression of 868 genes. The expression of standard markers such as GTP cyclohidrolase, MxA, and OAS isoenzymes A and B changed as a consequence of the action of IFN-β1a. Conclusions: This exhaustive and highly sensitive assay did not show differences in the genomic expression profile of these two products under the assayed experimental conditions. These results suggest that this technology might be useful for the initial comparison of biosimilars, being part of a comprehensive comparability program that includes clinical testing.
Fil: Sterin Prync, Aída Edith. Bio Sidus S.A.; Argentina
Fil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Bio Sidus S.A.; Argentina
Fil: Barrero, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Bello, R.. Bio Sidus S.A.; Argentina
Fil: Marangunich, L.. Bio Sidus S.A.; Argentina
Fil: Vidal, A.. Bio Sidus S.A.; Argentina
Fil: Criscuolo, M.. Bio Sidus S.A.; Argentina
Fil: Benasayag, L.. Centro Neurológico Integral ; Argentina
Fil: Famulari, A. L.. Fundación Argentina contra las Enfermedades Neurológicas del Envejecimiento; Argentina
Fil: Domínguez, R. O.. Fundación Argentina contra las Enfermedades Neurológicas del Envejecimiento; Argentina
Fil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Bio Sidus S.A.; Argentina
Fil: Diez, Roberto Alejandro. Bio Sidus S.A.; Argentina
description Objectives: Recombinant human interferon-beta (IFN-b) is a well-established treatment for multiple sclerosis (MS). The regulatory process for marketing authorization of biosimilars is currently under debate in certain countries. In the EU, EMEA has clearly defined the process including overarching and product-specific guidelines, which includes clinical testing. Biosimilarity needs to be based on comparability criteria, including at least molecular characterization, biological activity relevant for the therapeutic effect and relative bioavailability (“bioequivalence”). In the case of such complex diseases as MS, where the effect of treatment is not so directly measurable, in vitro tools can provide additional data to support comparability. Genomic microarrays assays might be useful to compare multisource biopharmaceuticals. The aim of the present study was to compare the pharmacodynamic genomic effects (in terms of transcriptional regulation) of two recombinant human IFN-β1a preparations on lymphocytes of multiple sclerosis patients using a whole genome microarray assay. Methods: We performed an ex vivo whole genome expression profiling of the effect of two preparations of IFN-β1a on non-adherent mononuclears from five relapsing-remitting MS patients analyzing microarrays (CodeLink™ Human Whole Genome). Patients blood was drawn, PBMCs isolated and cultured in three different conditions: culture medium (control), 1,000 U/ml of IFN-β1a (BLA- (STOFERON™, Bio Sidus) and 1,000 U/ml of IFN-β1a (REBIF™, Serono) RNA was purified from non-adherent cells (mostly lymphocytes), amplified and hybridized. Raw data were generated by CodeLink™ proprietary software. Data normalization, quality control and analysis of differential gene expression between treatments were done using linear model for microarray data. Functional annotation analysis of IFN-β1a MS treatment transcription was done using DAVID. Results: Out of the approximately 45,000 human sequences examined, no evidence of differential regulation was found when both treatments were compared (minimum adjusted p-value > 0.999). The IFN-β1a effect differentially regulated the expression of 868 genes. The expression of standard markers such as GTP cyclohidrolase, MxA, and OAS isoenzymes A and B changed as a consequence of the action of IFN-β1a. Conclusions: This exhaustive and highly sensitive assay did not show differences in the genomic expression profile of these two products under the assayed experimental conditions. These results suggest that this technology might be useful for the initial comparison of biosimilars, being part of a comprehensive comparability program that includes clinical testing.
publishDate 2008
dc.date.none.fl_str_mv 2008-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/137187
Sterin Prync, Aída Edith; Yankilevich, Patricio; Barrero, Paola Roxana; Bello, R.; Marangunich, L.; et al.; Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis; Dustri-Verlag Dr. Karl Feistle; International Journal of Clinical Pharmacology and Therapeutics; 46; 2; 2-2008; 64-71
0946-1965
CONICET Digital
CONICET
url http://hdl.handle.net/11336/137187
identifier_str_mv Sterin Prync, Aída Edith; Yankilevich, Patricio; Barrero, Paola Roxana; Bello, R.; Marangunich, L.; et al.; Two recombinant human interferon-beta 1a pharmaceutical preparations produce a similar transcriptional response determined using whole genome microarray analysis; Dustri-Verlag Dr. Karl Feistle; International Journal of Clinical Pharmacology and Therapeutics; 46; 2; 2-2008; 64-71
0946-1965
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.5414/cpp46064
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dc.publisher.none.fl_str_mv Dustri-Verlag Dr. Karl Feistle
publisher.none.fl_str_mv Dustri-Verlag Dr. Karl Feistle
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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