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Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms
Biologics have the potential to induce an immune response when used therapeutically. A number of in vitro assays are currently used preclinically to predict the risk of immunogenicity, but the validation of these preclinical tools suffers from the relatively small number of accessible immunogenic mo...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648324/ https://www.ncbi.nlm.nih.gov/pubmed/32370596 http://dx.doi.org/10.1080/19420862.2020.1764829 |
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author | Walsh, Robin E. Lannan, Megan Wen, Yi Wang, Xiaoli Moreland, Christopher A. Willency, Jill Knierman, Michael D. Spindler, Laura Liu, Ling Zeng, Wei Rocha, Guilherme V. Obungu, Victor Lu, Jirong Kaliyaperumal, Arunan Ferrante, Andrea Siegel, Robert Malherbe, Laurent P. |
author_facet | Walsh, Robin E. Lannan, Megan Wen, Yi Wang, Xiaoli Moreland, Christopher A. Willency, Jill Knierman, Michael D. Spindler, Laura Liu, Ling Zeng, Wei Rocha, Guilherme V. Obungu, Victor Lu, Jirong Kaliyaperumal, Arunan Ferrante, Andrea Siegel, Robert Malherbe, Laurent P. |
author_sort | Walsh, Robin E. |
collection | PubMed |
description | Biologics have the potential to induce an immune response when used therapeutically. A number of in vitro assays are currently used preclinically to predict the risk of immunogenicity, but the validation of these preclinical tools suffers from the relatively small number of accessible immunogenic molecules and the limited understanding of the mechanisms underlying the immunogenicity of biologics. Here, we present the post-hoc analysis of three monoclonal antibodies with high immunogenicity in the clinic. Two of the three antibodies elicited a CD4 T cell proliferative response in multiple donors in a peripheral blood mononuclear cell assay, but required different experimental conditions to induce these responses. The third antibody did not trigger any T cell response in this assay. These distinct capacities to promote CD4 T cell responses in vitro were mirrored by different capacities to stimulate innate immune cells. Only one of the three antibodies was capable of inducing human dendritic cell (DC) maturation; the second antibody promoted monocyte activation while the third one did not induce any innate cell activation in vitro. All three antibodies exhibited a moderate to high internalization by human DCs and MHC-associated peptide proteomics analysis revealed the presence of potential T cell epitopes that were confirmed by a T-cell proliferation assay. Collectively, these findings highlight the existence of distinct immune stimulatory mechanisms for immunogenic antibodies. These findings have implications for the preclinical immunogenicity risk assessment of biologics. |
format | Online Article Text |
id | pubmed-8648324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-86483242021-12-07 Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms Walsh, Robin E. Lannan, Megan Wen, Yi Wang, Xiaoli Moreland, Christopher A. Willency, Jill Knierman, Michael D. Spindler, Laura Liu, Ling Zeng, Wei Rocha, Guilherme V. Obungu, Victor Lu, Jirong Kaliyaperumal, Arunan Ferrante, Andrea Siegel, Robert Malherbe, Laurent P. MAbs Report Biologics have the potential to induce an immune response when used therapeutically. A number of in vitro assays are currently used preclinically to predict the risk of immunogenicity, but the validation of these preclinical tools suffers from the relatively small number of accessible immunogenic molecules and the limited understanding of the mechanisms underlying the immunogenicity of biologics. Here, we present the post-hoc analysis of three monoclonal antibodies with high immunogenicity in the clinic. Two of the three antibodies elicited a CD4 T cell proliferative response in multiple donors in a peripheral blood mononuclear cell assay, but required different experimental conditions to induce these responses. The third antibody did not trigger any T cell response in this assay. These distinct capacities to promote CD4 T cell responses in vitro were mirrored by different capacities to stimulate innate immune cells. Only one of the three antibodies was capable of inducing human dendritic cell (DC) maturation; the second antibody promoted monocyte activation while the third one did not induce any innate cell activation in vitro. All three antibodies exhibited a moderate to high internalization by human DCs and MHC-associated peptide proteomics analysis revealed the presence of potential T cell epitopes that were confirmed by a T-cell proliferation assay. Collectively, these findings highlight the existence of distinct immune stimulatory mechanisms for immunogenic antibodies. These findings have implications for the preclinical immunogenicity risk assessment of biologics. Taylor & Francis 2020-05-18 /pmc/articles/PMC8648324/ /pubmed/32370596 http://dx.doi.org/10.1080/19420862.2020.1764829 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Report Walsh, Robin E. Lannan, Megan Wen, Yi Wang, Xiaoli Moreland, Christopher A. Willency, Jill Knierman, Michael D. Spindler, Laura Liu, Ling Zeng, Wei Rocha, Guilherme V. Obungu, Victor Lu, Jirong Kaliyaperumal, Arunan Ferrante, Andrea Siegel, Robert Malherbe, Laurent P. Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms |
title | Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms |
title_full | Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms |
title_fullStr | Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms |
title_full_unstemmed | Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms |
title_short | Post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms |
title_sort | post-hoc assessment of the immunogenicity of three antibodies reveals distinct immune stimulatory mechanisms |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648324/ https://www.ncbi.nlm.nih.gov/pubmed/32370596 http://dx.doi.org/10.1080/19420862.2020.1764829 |
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