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Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates
Recently, we have developed a diphtheria toxin‐based recombinant anti‐human CCR4 immunotoxin for targeting CCR4(+) tumors and Tregs. In this study, we further optimized the dosing schedule for improved CCR4(+) Treg depletion. We have demonstrated that up to a 90% depletion was achieved and the deple...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068354/ https://www.ncbi.nlm.nih.gov/pubmed/29873181 http://dx.doi.org/10.1002/1878-0261.12331 |
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author | Wang, Zhaohui Louras, Nathan J. Lellouch, Alexandre G. Pratts, Shannon G. Zhang, Huiping Wang, Haoyu Huang, Christene A. Cetrulo, Curtis L. Madsen, Joren C. Sachs, David H. Wang, Zhirui |
author_facet | Wang, Zhaohui Louras, Nathan J. Lellouch, Alexandre G. Pratts, Shannon G. Zhang, Huiping Wang, Haoyu Huang, Christene A. Cetrulo, Curtis L. Madsen, Joren C. Sachs, David H. Wang, Zhirui |
author_sort | Wang, Zhaohui |
collection | PubMed |
description | Recently, we have developed a diphtheria toxin‐based recombinant anti‐human CCR4 immunotoxin for targeting CCR4(+) tumors and Tregs. In this study, we further optimized the dosing schedule for improved CCR4(+) Treg depletion. We have demonstrated that up to a 90% depletion was achieved and the depletion extended to approximately 2 weeks in the peripheral blood and more than 48 days in the lymph node at 25 μg·kg(−1), BID for 8 consecutive days in cynomolgus monkeys. Expansion was observed including monocytes and NK cells. Antibody against the CCR4 immunotoxin was detected after approximately 2 weeks, affecting further depletion efficacy for multiple course treatment. |
format | Online Article Text |
id | pubmed-6068354 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60683542018-08-03 Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates Wang, Zhaohui Louras, Nathan J. Lellouch, Alexandre G. Pratts, Shannon G. Zhang, Huiping Wang, Haoyu Huang, Christene A. Cetrulo, Curtis L. Madsen, Joren C. Sachs, David H. Wang, Zhirui Mol Oncol Research Articles Recently, we have developed a diphtheria toxin‐based recombinant anti‐human CCR4 immunotoxin for targeting CCR4(+) tumors and Tregs. In this study, we further optimized the dosing schedule for improved CCR4(+) Treg depletion. We have demonstrated that up to a 90% depletion was achieved and the depletion extended to approximately 2 weeks in the peripheral blood and more than 48 days in the lymph node at 25 μg·kg(−1), BID for 8 consecutive days in cynomolgus monkeys. Expansion was observed including monocytes and NK cells. Antibody against the CCR4 immunotoxin was detected after approximately 2 weeks, affecting further depletion efficacy for multiple course treatment. John Wiley and Sons Inc. 2018-07-03 2018-08 /pmc/articles/PMC6068354/ /pubmed/29873181 http://dx.doi.org/10.1002/1878-0261.12331 Text en © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Wang, Zhaohui Louras, Nathan J. Lellouch, Alexandre G. Pratts, Shannon G. Zhang, Huiping Wang, Haoyu Huang, Christene A. Cetrulo, Curtis L. Madsen, Joren C. Sachs, David H. Wang, Zhirui Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates |
title | Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates |
title_full | Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates |
title_fullStr | Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates |
title_full_unstemmed | Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates |
title_short | Dosing optimization of CCR4 immunotoxin for improved depletion of CCR4(+) Treg in nonhuman primates |
title_sort | dosing optimization of ccr4 immunotoxin for improved depletion of ccr4(+) treg in nonhuman primates |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068354/ https://www.ncbi.nlm.nih.gov/pubmed/29873181 http://dx.doi.org/10.1002/1878-0261.12331 |
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