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Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics

Immunogenicity, defined as the ability to provoke an immune response, can be either wanted (i.e., vaccines) or unwanted. The latter refers to an immune response to protein or peptide therapeutics, characterized by the production of anti-drug antibodies, which may affect the efficacy and/or the safet...

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Autores principales: Siegel, Michel, Steiner, Guido, Franssen, Linnea C., Carratu, Francesca, Herron, James, Hartman, Katharina, Looney, Cary M., Ducret, Axel, Bray-French, Katharine, Rohr, Olivier, Hickling, Timothy P., Smith, Noel, Marban-Doran, Céline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781343/
https://www.ncbi.nlm.nih.gov/pubmed/36559166
http://dx.doi.org/10.3390/pharmaceutics14122672
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author Siegel, Michel
Steiner, Guido
Franssen, Linnea C.
Carratu, Francesca
Herron, James
Hartman, Katharina
Looney, Cary M.
Ducret, Axel
Bray-French, Katharine
Rohr, Olivier
Hickling, Timothy P.
Smith, Noel
Marban-Doran, Céline
author_facet Siegel, Michel
Steiner, Guido
Franssen, Linnea C.
Carratu, Francesca
Herron, James
Hartman, Katharina
Looney, Cary M.
Ducret, Axel
Bray-French, Katharine
Rohr, Olivier
Hickling, Timothy P.
Smith, Noel
Marban-Doran, Céline
author_sort Siegel, Michel
collection PubMed
description Immunogenicity, defined as the ability to provoke an immune response, can be either wanted (i.e., vaccines) or unwanted. The latter refers to an immune response to protein or peptide therapeutics, characterized by the production of anti-drug antibodies, which may affect the efficacy and/or the safety profiles of these drugs. Consequently, evaluation of the risk of immunogenicity early in the development of biotherapeutics is of critical importance for defining their efficacy and safety profiles. Here, we describe and validate a fit-for-purpose FluoroSpot-based in vitro assay for the evaluation of drug-specific T cell responses. A panel of 24 biotherapeutics with a wide range of clinical anti-drug antibody response rates were tested in this assay. We demonstrated that using suitable cutoffs and donor cohort sizes, this assay could identify most of the compounds with high clinical immunogenicity rates (71% and 78% for sensitivity and specificity, respectively) while we characterized the main sources of assay variability. Overall, these data indicate that the dendritic cell and CD4+ T cell restimulation assay published herein could be a valuable tool to assess the risk of drug-specific T cell responses and contribute to the selection of clinical candidates in early development.
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spelling pubmed-97813432022-12-24 Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics Siegel, Michel Steiner, Guido Franssen, Linnea C. Carratu, Francesca Herron, James Hartman, Katharina Looney, Cary M. Ducret, Axel Bray-French, Katharine Rohr, Olivier Hickling, Timothy P. Smith, Noel Marban-Doran, Céline Pharmaceutics Article Immunogenicity, defined as the ability to provoke an immune response, can be either wanted (i.e., vaccines) or unwanted. The latter refers to an immune response to protein or peptide therapeutics, characterized by the production of anti-drug antibodies, which may affect the efficacy and/or the safety profiles of these drugs. Consequently, evaluation of the risk of immunogenicity early in the development of biotherapeutics is of critical importance for defining their efficacy and safety profiles. Here, we describe and validate a fit-for-purpose FluoroSpot-based in vitro assay for the evaluation of drug-specific T cell responses. A panel of 24 biotherapeutics with a wide range of clinical anti-drug antibody response rates were tested in this assay. We demonstrated that using suitable cutoffs and donor cohort sizes, this assay could identify most of the compounds with high clinical immunogenicity rates (71% and 78% for sensitivity and specificity, respectively) while we characterized the main sources of assay variability. Overall, these data indicate that the dendritic cell and CD4+ T cell restimulation assay published herein could be a valuable tool to assess the risk of drug-specific T cell responses and contribute to the selection of clinical candidates in early development. MDPI 2022-12-01 /pmc/articles/PMC9781343/ /pubmed/36559166 http://dx.doi.org/10.3390/pharmaceutics14122672 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Siegel, Michel
Steiner, Guido
Franssen, Linnea C.
Carratu, Francesca
Herron, James
Hartman, Katharina
Looney, Cary M.
Ducret, Axel
Bray-French, Katharine
Rohr, Olivier
Hickling, Timothy P.
Smith, Noel
Marban-Doran, Céline
Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics
title Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics
title_full Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics
title_fullStr Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics
title_full_unstemmed Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics
title_short Validation of a Dendritic Cell and CD4+ T Cell Restimulation Assay Contributing to the Immunogenicity Risk Evaluation of Biotherapeutics
title_sort validation of a dendritic cell and cd4+ t cell restimulation assay contributing to the immunogenicity risk evaluation of biotherapeutics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781343/
https://www.ncbi.nlm.nih.gov/pubmed/36559166
http://dx.doi.org/10.3390/pharmaceutics14122672
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