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Harnessing the power of antibodies to fight bone metastasis
Antibody-based therapies have proved to be of great value in cancer treatment. Despite the clinical success of these biopharmaceuticals, reaching targets in the bone microenvironment has proved to be difficult due to the relatively low vascularization of bone tissue and the presence of physical barr...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221630/ https://www.ncbi.nlm.nih.gov/pubmed/34162538 http://dx.doi.org/10.1126/sciadv.abf2051 |
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author | Tian, Zeru Wu, Ling Yu, Chenfei Chen, Yuda Xu, Zhan Bado, Igor Loredo, Axel Wang, Lushun Wang, Hai Wu, Kuan-Lin Zhang, Weijie Zhang, Xiang H.-F. Xiao, Han |
author_facet | Tian, Zeru Wu, Ling Yu, Chenfei Chen, Yuda Xu, Zhan Bado, Igor Loredo, Axel Wang, Lushun Wang, Hai Wu, Kuan-Lin Zhang, Weijie Zhang, Xiang H.-F. Xiao, Han |
author_sort | Tian, Zeru |
collection | PubMed |
description | Antibody-based therapies have proved to be of great value in cancer treatment. Despite the clinical success of these biopharmaceuticals, reaching targets in the bone microenvironment has proved to be difficult due to the relatively low vascularization of bone tissue and the presence of physical barriers. Here, we have used an innovative bone-targeting (BonTarg) technology to generate a first-in-class bone-targeting antibody. Our strategy involves the use of pClick antibody conjugation technology to chemically couple the bone-targeting moiety bisphosphonate to therapeutic antibodies. Bisphosphonate modification of these antibodies results in the delivery of higher conjugate concentrations to the bone metastatic niche, relative to other tissues. In xenograft mice models, this strategy provides enhanced inhibition of bone metastases and multiorgan secondary metastases that arise from bone lesions. Specific delivery of therapeutic antibodies to the bone, therefore, represents a promising strategy for the treatment of bone metastatic cancers and other bone diseases. |
format | Online Article Text |
id | pubmed-8221630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82216302021-07-01 Harnessing the power of antibodies to fight bone metastasis Tian, Zeru Wu, Ling Yu, Chenfei Chen, Yuda Xu, Zhan Bado, Igor Loredo, Axel Wang, Lushun Wang, Hai Wu, Kuan-Lin Zhang, Weijie Zhang, Xiang H.-F. Xiao, Han Sci Adv Research Articles Antibody-based therapies have proved to be of great value in cancer treatment. Despite the clinical success of these biopharmaceuticals, reaching targets in the bone microenvironment has proved to be difficult due to the relatively low vascularization of bone tissue and the presence of physical barriers. Here, we have used an innovative bone-targeting (BonTarg) technology to generate a first-in-class bone-targeting antibody. Our strategy involves the use of pClick antibody conjugation technology to chemically couple the bone-targeting moiety bisphosphonate to therapeutic antibodies. Bisphosphonate modification of these antibodies results in the delivery of higher conjugate concentrations to the bone metastatic niche, relative to other tissues. In xenograft mice models, this strategy provides enhanced inhibition of bone metastases and multiorgan secondary metastases that arise from bone lesions. Specific delivery of therapeutic antibodies to the bone, therefore, represents a promising strategy for the treatment of bone metastatic cancers and other bone diseases. American Association for the Advancement of Science 2021-06-23 /pmc/articles/PMC8221630/ /pubmed/34162538 http://dx.doi.org/10.1126/sciadv.abf2051 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 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 (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Tian, Zeru Wu, Ling Yu, Chenfei Chen, Yuda Xu, Zhan Bado, Igor Loredo, Axel Wang, Lushun Wang, Hai Wu, Kuan-Lin Zhang, Weijie Zhang, Xiang H.-F. Xiao, Han Harnessing the power of antibodies to fight bone metastasis |
title | Harnessing the power of antibodies to fight bone metastasis |
title_full | Harnessing the power of antibodies to fight bone metastasis |
title_fullStr | Harnessing the power of antibodies to fight bone metastasis |
title_full_unstemmed | Harnessing the power of antibodies to fight bone metastasis |
title_short | Harnessing the power of antibodies to fight bone metastasis |
title_sort | harnessing the power of antibodies to fight bone metastasis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221630/ https://www.ncbi.nlm.nih.gov/pubmed/34162538 http://dx.doi.org/10.1126/sciadv.abf2051 |
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