Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy. Author Hanqiu Zheng, Yangjin Bae, Sabine Kasimir-Bauer, Rebecca Tang, Jin Chen, Guangwen Ren, Min Yuan, Mark Esposito, Wenyang Li, Yong Wei, Minhong Shen, Lanjing Zhang, Nikolai Tupitsyn, Klaus Pantel, Chadwick King, Jan Sun, Jodi Moriguchi, Helen Jun, Angela Coxon, Brendan Lee, Yibin Kang Publication Year 2017 Type Journal Article Abstract Bone metastasis is a major health threat to breast cancer patients. Tumor-derived Jagged1 represents a central node in mediating tumor-stromal interactions that promote osteolytic bone metastasis. Here, we report the development of a highly effective fully human monoclonal antibody against Jagged1 (clone 15D11). In addition to its inhibitory effect on bone metastasis of Jagged1-expressing tumor cells, 15D11 dramatically sensitizes bone metastasis to chemotherapy, which induces Jagged1 expression in osteoblasts to provide a survival niche for cancer cells. We further confirm the bone metastasis-promoting function of osteoblast-derived Jagged1 using osteoblast-specific Jagged1 transgenic mouse model. These findings establish 15D11 as a potential therapeutic agent for the prevention or treatment of bone metastasis. Keywords Animals, Mice, Humans, Mice, Transgenic, Bone Neoplasms, Antineoplastic Agents, Jagged-1 Protein, Xenograft Model Antitumor Assays, Osteoblasts, Antibodies, Monoclonal Journal Cancer Cell Volume 32 Issue 6 Pages 731-747.e6 Date Published 2017 Dec 11 ISSN Number 1878-3686 DOI 10.1016/j.ccell.2017.11.002 Alternate Journal Cancer Cell PMCID PMC5729937 PMID 29232552 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML