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

ABSTRACT: Despite 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 activit

SUBMITTER: Tian Z 

PROVIDER: S-EPMC8961797 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature