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Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics

An In Vitro Comparative Immunogenicity Assessment (IVCIA) assay was evaluated as a tool for predicting the potential relative immunogenicity of biotherapeutic attributes. Peripheral blood mononuclear cells from up to 50 healthy naïve human donors were monitored up to 8 days for T-cell proliferation,...

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Autores principales: Joubert, Marisa K., Deshpande, Meghana, Yang, Jane, Reynolds, Helen, Bryson, Christine, Fogg, Mark, Baker, Matthew P., Herskovitz, Jonathan, Goletz, Theresa J., Zhou, Lei, Moxness, Michael, Flynn, Gregory C., Narhi, Linda O., Jawa, Vibha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975389/
https://www.ncbi.nlm.nih.gov/pubmed/27494246
http://dx.doi.org/10.1371/journal.pone.0159328
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author Joubert, Marisa K.
Deshpande, Meghana
Yang, Jane
Reynolds, Helen
Bryson, Christine
Fogg, Mark
Baker, Matthew P.
Herskovitz, Jonathan
Goletz, Theresa J.
Zhou, Lei
Moxness, Michael
Flynn, Gregory C.
Narhi, Linda O.
Jawa, Vibha
author_facet Joubert, Marisa K.
Deshpande, Meghana
Yang, Jane
Reynolds, Helen
Bryson, Christine
Fogg, Mark
Baker, Matthew P.
Herskovitz, Jonathan
Goletz, Theresa J.
Zhou, Lei
Moxness, Michael
Flynn, Gregory C.
Narhi, Linda O.
Jawa, Vibha
author_sort Joubert, Marisa K.
collection PubMed
description An In Vitro Comparative Immunogenicity Assessment (IVCIA) assay was evaluated as a tool for predicting the potential relative immunogenicity of biotherapeutic attributes. Peripheral blood mononuclear cells from up to 50 healthy naïve human donors were monitored up to 8 days for T-cell proliferation, the number of IL-2 or IFN-γ secreting cells, and the concentration of a panel of secreted cytokines. The response in the assay to 10 monoclonal antibodies was found to be in agreement with the clinical immunogenicity, suggesting that the assay might be applied to immunogenicity risk assessment of antibody biotherapeutic attributes. However, the response in the assay is a measure of T-cell functional activity and the alignment with clinical immunogenicity depends on several other factors. The assay was sensitive to sequence variants and could differentiate single point mutations of the same biotherapeutic. Nine mAbs that were highly aggregated by stirring induced a higher response in the assay than the original mAbs before stirring stress, in a manner that did not match the relative T-cell response of the original mAbs. In contrast, mAbs that were glycated by different sugars (galactose, glucose, and mannose) showed little to no increase in response in the assay above the response to the original mAbs before glycation treatment. The assay was also used successfully to assess similarity between multiple lots of the same mAb, both from the same manufacturer and from different manufacturers (biosimilars). A strategy for using the IVCIA assay for immunogenicity risk assessment during the entire lifespan development of biopharmaceuticals is proposed.
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spelling pubmed-49753892016-08-25 Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics Joubert, Marisa K. Deshpande, Meghana Yang, Jane Reynolds, Helen Bryson, Christine Fogg, Mark Baker, Matthew P. Herskovitz, Jonathan Goletz, Theresa J. Zhou, Lei Moxness, Michael Flynn, Gregory C. Narhi, Linda O. Jawa, Vibha PLoS One Research Article An In Vitro Comparative Immunogenicity Assessment (IVCIA) assay was evaluated as a tool for predicting the potential relative immunogenicity of biotherapeutic attributes. Peripheral blood mononuclear cells from up to 50 healthy naïve human donors were monitored up to 8 days for T-cell proliferation, the number of IL-2 or IFN-γ secreting cells, and the concentration of a panel of secreted cytokines. The response in the assay to 10 monoclonal antibodies was found to be in agreement with the clinical immunogenicity, suggesting that the assay might be applied to immunogenicity risk assessment of antibody biotherapeutic attributes. However, the response in the assay is a measure of T-cell functional activity and the alignment with clinical immunogenicity depends on several other factors. The assay was sensitive to sequence variants and could differentiate single point mutations of the same biotherapeutic. Nine mAbs that were highly aggregated by stirring induced a higher response in the assay than the original mAbs before stirring stress, in a manner that did not match the relative T-cell response of the original mAbs. In contrast, mAbs that were glycated by different sugars (galactose, glucose, and mannose) showed little to no increase in response in the assay above the response to the original mAbs before glycation treatment. The assay was also used successfully to assess similarity between multiple lots of the same mAb, both from the same manufacturer and from different manufacturers (biosimilars). A strategy for using the IVCIA assay for immunogenicity risk assessment during the entire lifespan development of biopharmaceuticals is proposed. Public Library of Science 2016-08-05 /pmc/articles/PMC4975389/ /pubmed/27494246 http://dx.doi.org/10.1371/journal.pone.0159328 Text en © 2016 Joubert et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Joubert, Marisa K.
Deshpande, Meghana
Yang, Jane
Reynolds, Helen
Bryson, Christine
Fogg, Mark
Baker, Matthew P.
Herskovitz, Jonathan
Goletz, Theresa J.
Zhou, Lei
Moxness, Michael
Flynn, Gregory C.
Narhi, Linda O.
Jawa, Vibha
Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics
title Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics
title_full Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics
title_fullStr Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics
title_full_unstemmed Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics
title_short Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based Biotherapeutics
title_sort use of in vitro assays to assess immunogenicity risk of antibody-based biotherapeutics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975389/
https://www.ncbi.nlm.nih.gov/pubmed/27494246
http://dx.doi.org/10.1371/journal.pone.0159328
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