Over the past 30 years, antibody-based therapies against cancer have been developed and proved to be successful in the clinic. Despite their clinical success, delivery of these antibodies to the bone niche has proven to be difficult due to relatively low vascularization and the physical barriers of penetration. Inspired by the bone-targeting mechanism of natural biomolecules, we have developed an innovative bone targeting (BonTarg) technology that enables the preparation of antibodies with both antigen and bone specificity. The resulting bone-targeting antibodies exhibit improved in vivo therapeutic efficacy in the treatment of breast cancer micrometastasis and in the prevention of secondary metastatic dissemination from the initial bone lesions. This study establishes a new strategy for transitioning antibody-based therapies from antigen-specific to both antigen and tissue-specific, thus providing a promising new avenue for advancing antibody therapy toward clinical translation.
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