1区 · 医学
Article
作者: Lee, Brendan ; Wei, Yong ; Chen, Jin ; Coxon, Angela ; Ren, Guangwen ; Yuan, Min ; Shen, Minhong ; Esposito, Mark ; Zhang, Lanjing ; Zheng, Hanqiu ; Kang, Yibin ; King, Chadwick ; Jun, Helen Toni ; Li, Wenyang ; Tang, Rebecca ; Moriguchi, Jodi ; Bae, Yangjin ; Tupitsyn, Nikolai ; Sun, Jan ; Kasimir-Bauer, Sabine ; Pantel, Klaus
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.