Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy.

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.

Journal
Cancer Cell
Volume
32
Issue
6
Pages
731-747.e6
Date Published
2017 Dec 11
ISSN Number
1878-3686
Alternate Journal
Cancer Cell
PMCID
PMC5729937
PMID
29232552