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Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates
In this study we compared the pharmacokinetic profile of four unrelated antibodies, which do not bind to mammalian antigens, in IgG1 and IgG2 frameworks in both rats and non-human primates (NHP). This allowed for extensive cross comparison of the impact of antibody isotype, complementarity determini...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533040/ https://www.ncbi.nlm.nih.gov/pubmed/31120944 http://dx.doi.org/10.1371/journal.pone.0217061 |
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author | Walker, Kenneth W. Salimi-Moosavi, Hossein Arnold, Gregory E. Chen, Qing Soto, Marcus Jacobsen, Frederick W. Hui, John |
author_facet | Walker, Kenneth W. Salimi-Moosavi, Hossein Arnold, Gregory E. Chen, Qing Soto, Marcus Jacobsen, Frederick W. Hui, John |
author_sort | Walker, Kenneth W. |
collection | PubMed |
description | In this study we compared the pharmacokinetic profile of four unrelated antibodies, which do not bind to mammalian antigens, in IgG1 and IgG2 frameworks in both rats and non-human primates (NHP). This allowed for extensive cross comparison of the impact of antibody isotype, complementarity determining regions (CDR) and model species on pharmacokinetics without the confounding influence of antigen binding in the hosts. While antibody isotype had no significant impact on the pharmacokinetics, the CDRs do alter the profile, and there is an inverse correlation between the neonatal Fc receptor (FcRn) affinity and pharmacokinetic performance. Faster clearance rates were also associated with higher isoelectric points; however, although this panel of antibodies all possess basic isoelectric points, ranging from 8.44 to 9.18, they also have exceptional in vivo half-lives, averaging 369 hours, and low clearance rates, averaging 0.18 ml/h/kg in NHPs. This pattern of pharmacokinetic characteristics was conserved between rats and NHPs. |
format | Online Article Text |
id | pubmed-6533040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65330402019-06-05 Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates Walker, Kenneth W. Salimi-Moosavi, Hossein Arnold, Gregory E. Chen, Qing Soto, Marcus Jacobsen, Frederick W. Hui, John PLoS One Research Article In this study we compared the pharmacokinetic profile of four unrelated antibodies, which do not bind to mammalian antigens, in IgG1 and IgG2 frameworks in both rats and non-human primates (NHP). This allowed for extensive cross comparison of the impact of antibody isotype, complementarity determining regions (CDR) and model species on pharmacokinetics without the confounding influence of antigen binding in the hosts. While antibody isotype had no significant impact on the pharmacokinetics, the CDRs do alter the profile, and there is an inverse correlation between the neonatal Fc receptor (FcRn) affinity and pharmacokinetic performance. Faster clearance rates were also associated with higher isoelectric points; however, although this panel of antibodies all possess basic isoelectric points, ranging from 8.44 to 9.18, they also have exceptional in vivo half-lives, averaging 369 hours, and low clearance rates, averaging 0.18 ml/h/kg in NHPs. This pattern of pharmacokinetic characteristics was conserved between rats and NHPs. Public Library of Science 2019-05-23 /pmc/articles/PMC6533040/ /pubmed/31120944 http://dx.doi.org/10.1371/journal.pone.0217061 Text en © 2019 Walker 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 Walker, Kenneth W. Salimi-Moosavi, Hossein Arnold, Gregory E. Chen, Qing Soto, Marcus Jacobsen, Frederick W. Hui, John Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates |
title | Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates |
title_full | Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates |
title_fullStr | Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates |
title_full_unstemmed | Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates |
title_short | Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates |
title_sort | pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched igg1 and igg2 isotypes in rodents and non-human primates |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533040/ https://www.ncbi.nlm.nih.gov/pubmed/31120944 http://dx.doi.org/10.1371/journal.pone.0217061 |
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