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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
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.
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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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