Journal
SCIENCE ADVANCES
Volume 7, Issue 26, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abf2051
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Funding
- Cancer Prevention Research Institute of Texas [CPRIT RR170014]
- NIH [GM133706, AI165079, CA255894, CA183878, CA251950, CA221946]
- Robert A. Welch Foundation [C-1970]
- U.S. Department of Defense [BC201371]
- U.S. Department of Defense (DAMD) [W81XWH-16-1-0073]
- John S. Dunn Foundation Collaborative Research Award
- Hamill Innovation Award
- Breast Cancer Research Foundation
- McNair Medical Institute
- U.S. Department of Defense (Era of Hope Scholarship)
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The use of bone-targeting technology to chemically couple bisphosphonate compounds to therapeutic antibodies enhances the delivery of conjugates to bone metastatic niches, providing enhanced inhibition of bone and multiorgan secondary metastases. Specific delivery of therapeutic antibodies to the bone represents a promising strategy for the treatment of bone metastatic cancers and other bone diseases.
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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