Wnt 通路是参与干细胞稳态和组织再生的进化保守通路。 Wnt 通路中的异常信号传导与癌症高度相关。开发抗体来阻止卷曲受体 (FZD)（Wnt 通路中的主要受体）的过度激活是治疗癌症的可行选择之一。然而，由于 10 个 FZD 之间具有高度同源性，获得异构体特异性抗体通常具有挑战性。在本研究中，通过使用合成文库，我们鉴定了一种名为 pF8_AC3 的抗体，该抗体优先与 FZD8 结合。以pF8_AC3和FZD8复合物的结构为指导，进一步构建第二代靶向文库，最终获得FZD8特异性抗体sF8_AG6。基于细胞的检测表明这些抗体可以选择性地阻断 FZD8 介导的信号激活。总而言之，这些抗体有潜力在未来开发成治疗药物。版权所有 © 2023。由 Elsevier B.V. 出版。

The Wnt pathway is an evolutionarily conserved pathway involved in stem cell homeostasis and tissue regeneration. Aberrant signaling in the Wnt pathway is highly associated with cancer. Developing antibodies to block overactivation of Frizzled receptors (FZDs), the main receptors in the Wnt pathway, is one of the viable options for treating cancer. However, obtaining isoform-specific antibodies is often challenging due to the high degree of homology among the ten FZDs. In this study, by using a synthetic library, we identified an antibody named pF8_AC3 that preferentially binds to FZD8. Guided by the structure of the complex of pF8_AC3 and FZD8, a second-generation targeted library was further constructed, and finally, the FZD8-specific antibody sF8_AG6 was obtained. Cell-based assays showed that these antibodies could selectively block FZD8-mediated signaling activation. Taken together, these antibodies have the potential to be developed into therapeutic drugs in the future.Copyright © 2023. Published by Elsevier B.V.