OncoMed Pharmaceuticals, Redwood City, CA 94063, USA.
Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11717-22. doi: 10.1073/pnas.1120068109. Epub 2012 Jul 2.
The Wnt/β-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, interacts with five Fzd receptors through a conserved epitope within the extracellular domain and blocks canonical Wnt signaling induced by multiple Wnt family members. In xenograft studies with minimally passaged human tumors, this antibody inhibits the growth of a range of tumor types, reduces tumor-initiating cell frequency, and exhibits synergistic activity with standard-of-care chemotherapeutic agents.
Wnt/β-catenin 通路通过 Frizzled（Fzd）受体家族和几个核心受体传递信号，长期以来一直与癌症有关。在这里，我们展示了一种用单克隆抗体 OMP-18R5 靶向 Wnt 通路的治疗方法。这种抗体最初通过与 Frizzled 7 结合而被鉴定出来，通过细胞外结构域内的保守表位与五个 Fzd 受体相互作用，并阻断多种 Wnt 家族成员诱导的经典 Wnt 信号。在用人源肿瘤的最小传代进行的异种移植研究中，该抗体抑制了一系列肿瘤类型的生长，降低了肿瘤起始细胞的频率，并与标准护理化疗药物具有协同作用。
