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Immunogenicity Risk Profile of Nanobodies
Nanobodies (Nbs), the variable domains of camelid heavy chain-only antibodies, are a promising class of therapeutics or in vivo imaging reagents entering the clinic. They possess unique characteristics, including a minimal size, providing fast pharmacokinetics, high-target specificity, and an affini...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985456/ https://www.ncbi.nlm.nih.gov/pubmed/33767701 http://dx.doi.org/10.3389/fimmu.2021.632687 |
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author | Ackaert, Chloé Smiejkowska, Natalia Xavier, Catarina Sterckx, Yann G. J. Denies, Sofie Stijlemans, Benoit Elkrim, Yvon Devoogdt, Nick Caveliers, Vicky Lahoutte, Tony Muyldermans, Serge Breckpot, Karine Keyaerts, Marleen |
author_facet | Ackaert, Chloé Smiejkowska, Natalia Xavier, Catarina Sterckx, Yann G. J. Denies, Sofie Stijlemans, Benoit Elkrim, Yvon Devoogdt, Nick Caveliers, Vicky Lahoutte, Tony Muyldermans, Serge Breckpot, Karine Keyaerts, Marleen |
author_sort | Ackaert, Chloé |
collection | PubMed |
description | Nanobodies (Nbs), the variable domains of camelid heavy chain-only antibodies, are a promising class of therapeutics or in vivo imaging reagents entering the clinic. They possess unique characteristics, including a minimal size, providing fast pharmacokinetics, high-target specificity, and an affinity in the (sub-)nanomolar range in conjunction with an easy selection and production, which allow them to outperform conventional antibodies for imaging and radiotherapeutic purposes. As for all protein theranostics, extended safety assessment and investigation of their possible immunogenicity in particular are required. In this study, we assessed the immunogenicity risk profile of two Nbs that are in phase II clinical trials: a first Nb against Human Epidermal growth factor Receptor 2 (HER2) for PET imaging of breast cancer and a second Nb with specificity to the Macrophage Mannose Receptor (MMR) for PET imaging of tumor-associated macrophages. For the anti-HER2 Nb, we show that only one out of 20 patients had a low amount of pre-existing anti-drug antibodies (ADAs), which only marginally increased 3 months after administering the Nb, and without negative effects of safety and pharmacokinetics. Further in vitro immunogenicity assessment assays showed that both non-humanized Nbs were taken up by human dendritic cells but exhibited no or only a marginal capacity to activate dendritic cells or to induce T cell proliferation. From our data, we conclude that monomeric Nbs present a low immunogenicity risk profile, which is encouraging for their future development toward potential clinical applications. ONE SENTENCE SUMMARY: Nanobodies, the recombinant single domain affinity reagents derived from heavy chain-only antibodies in camelids, are proven to possess a low immunogenicity risk profile, which will facilitate a growing number of Nanobodies to enter the clinic for therapeutic or in vivo diagnostic applications. |
format | Online Article Text |
id | pubmed-7985456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79854562021-03-24 Immunogenicity Risk Profile of Nanobodies Ackaert, Chloé Smiejkowska, Natalia Xavier, Catarina Sterckx, Yann G. J. Denies, Sofie Stijlemans, Benoit Elkrim, Yvon Devoogdt, Nick Caveliers, Vicky Lahoutte, Tony Muyldermans, Serge Breckpot, Karine Keyaerts, Marleen Front Immunol Immunology Nanobodies (Nbs), the variable domains of camelid heavy chain-only antibodies, are a promising class of therapeutics or in vivo imaging reagents entering the clinic. They possess unique characteristics, including a minimal size, providing fast pharmacokinetics, high-target specificity, and an affinity in the (sub-)nanomolar range in conjunction with an easy selection and production, which allow them to outperform conventional antibodies for imaging and radiotherapeutic purposes. As for all protein theranostics, extended safety assessment and investigation of their possible immunogenicity in particular are required. In this study, we assessed the immunogenicity risk profile of two Nbs that are in phase II clinical trials: a first Nb against Human Epidermal growth factor Receptor 2 (HER2) for PET imaging of breast cancer and a second Nb with specificity to the Macrophage Mannose Receptor (MMR) for PET imaging of tumor-associated macrophages. For the anti-HER2 Nb, we show that only one out of 20 patients had a low amount of pre-existing anti-drug antibodies (ADAs), which only marginally increased 3 months after administering the Nb, and without negative effects of safety and pharmacokinetics. Further in vitro immunogenicity assessment assays showed that both non-humanized Nbs were taken up by human dendritic cells but exhibited no or only a marginal capacity to activate dendritic cells or to induce T cell proliferation. From our data, we conclude that monomeric Nbs present a low immunogenicity risk profile, which is encouraging for their future development toward potential clinical applications. ONE SENTENCE SUMMARY: Nanobodies, the recombinant single domain affinity reagents derived from heavy chain-only antibodies in camelids, are proven to possess a low immunogenicity risk profile, which will facilitate a growing number of Nanobodies to enter the clinic for therapeutic or in vivo diagnostic applications. Frontiers Media S.A. 2021-03-09 /pmc/articles/PMC7985456/ /pubmed/33767701 http://dx.doi.org/10.3389/fimmu.2021.632687 Text en Copyright © 2021 Ackaert, Smiejkowska, Xavier, Sterckx, Denies, Stijlemans, Elkrim, Devoogdt, Caveliers, Lahoutte, Muyldermans, Breckpot and Keyaerts. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ackaert, Chloé Smiejkowska, Natalia Xavier, Catarina Sterckx, Yann G. J. Denies, Sofie Stijlemans, Benoit Elkrim, Yvon Devoogdt, Nick Caveliers, Vicky Lahoutte, Tony Muyldermans, Serge Breckpot, Karine Keyaerts, Marleen Immunogenicity Risk Profile of Nanobodies |
title | Immunogenicity Risk Profile of Nanobodies |
title_full | Immunogenicity Risk Profile of Nanobodies |
title_fullStr | Immunogenicity Risk Profile of Nanobodies |
title_full_unstemmed | Immunogenicity Risk Profile of Nanobodies |
title_short | Immunogenicity Risk Profile of Nanobodies |
title_sort | immunogenicity risk profile of nanobodies |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985456/ https://www.ncbi.nlm.nih.gov/pubmed/33767701 http://dx.doi.org/10.3389/fimmu.2021.632687 |
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