1. Harnessing the power of antibodies to fight bone metastasis
- Author
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Igor Bado, Weijie Zhang, Chenfei Yu, Kuan-Lin Wu, Lushun Wang, Zhan Xu, Zeru Tian, Xiang Zhang, Yuda Chen, Axel Loredo, Ling Wu, Hai Wang, and Han Xiao
- Subjects
medicine.medical_treatment ,Bone Neoplasms ,Bone tissue ,Biochemistry ,Antibodies ,Bone and Bones ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Metastatic niche ,Trastuzumab ,medicine ,Tumor Microenvironment ,Animals ,Humans ,Neoplasm Metastasis ,Human Epidermal Growth Factor Receptor 2 ,Research Articles ,030304 developmental biology ,Cancer ,0303 health sciences ,Multidisciplinary ,biology ,Diphosphonates ,business.industry ,Bone metastasis ,SciAdv r-articles ,Life Sciences ,Bisphosphonate ,medicine.disease ,Cancer treatment ,medicine.anatomical_structure ,Bone targeting ,Physical Barrier ,Bone lesion ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Heterografts ,Antibody ,business ,medicine.drug ,Research Article - Abstract
Precision modification of antibodies with bone-targeting moieties unleashes their potential for the treatment of bone metastases., 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.
- Published
- 2020