Bone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Bone

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dc.citation.firstpage312en_US
dc.citation.issueNumber3en_US
dc.citation.journalTitleACS Central Scienceen_US
dc.citation.lastpage321en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorTian, Zeruen_US
dc.contributor.authorYu, Chenfeien_US
dc.contributor.authorZhang, Weijieen_US
dc.contributor.authorWu, Kuan-Linen_US
dc.contributor.authorWang, Chenhangen_US
dc.contributor.authorGupta, Ruchien_US
dc.contributor.authorXu, Zhanen_US
dc.contributor.authorWu, Lingen_US
dc.contributor.authorChen, Yudaen_US
dc.contributor.authorZhang, Xiang H.-F.en_US
dc.contributor.authorXiao, Hanen_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgBiosciencesen_US
dc.contributor.orgChemistryen_US
dc.date.accessioned2022-04-28T14:29:01Zen_US
dc.date.available2022-04-28T14:29:01Zen_US
dc.date.issued2022en_US
dc.description.abstractDespite the rapid evolution of therapeutic antibodies, their clinical efficacy in the treatment of bone tumors is hampered due to the inadequate pharmacokinetics and poor bone tissue accessibility of these large macromolecules. Here, we show that engineering therapeutic antibodies with bone-homing peptide sequences dramatically enhances their concentrations in the bone metastatic niche, resulting in significantly reduced survival and progression of breast cancer bone metastases. To enhance the bone tumor-targeting ability of engineered antibodies, we introduced varying numbers of bone-homing peptides into permissive sites of the anti-HER2 antibody, trastuzumab. Compared to the unmodified antibody, the engineered antibodies have similar pharmacokinetics and in vitro cytotoxic activity, but exhibit improved bone tumor distribution in vivo. Accordingly, in xenograft models of breast cancer metastasis to bone sites, engineered antibodies with enhanced bone specificity exhibit increased inhibition of both initial bone metastases and secondary multiorgan metastases. Furthermore, this engineering strategy is also applied to prepare bone-targeting antibody–drug conjugates with enhanced therapeutic efficacy. These results demonstrate that adding bone-specific targeting to antibody therapy results in robust bone tumor delivery efficacy. This provides a powerful strategy to overcome the poor accessibility of antibodies to the bone tumors and the consequential resistance to the therapy.en_US
dc.identifier.citationTian, Zeru, Yu, Chenfei, Zhang, Weijie, et al.. "Bone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Bone." <i>ACS Central Science,</i> 8, no. 3 (2022) American Chemical Society: 312-321. https://doi.org/10.1021/acscentsci.1c01024.en_US
dc.identifier.digitalacscentsci-1c01024en_US
dc.identifier.doihttps://doi.org/10.1021/acscentsci.1c01024en_US
dc.identifier.urihttps://hdl.handle.net/1911/112182en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleBone-Specific Enhancement of Antibody Therapy for Breast Cancer Metastasis to Boneen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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