Harnessing the power of antibodies to fight bone metastasis

Zeru Tian, Ling Wu, Chenfei Yu, Yuda Chen, Zhan Xu, Igor Bado, Axel Loredo, Lushun Wang, Hai Wang, Kuan Lin Wu, Weijie Zhang, Xiang H.F. Zhang, Han Xiao

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Article numbereabf2051
JournalScience advances
Volume7
Issue number26
DOIs
StatePublished - Jun 2021
Externally publishedYes

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