Using apelin-based synthetic Notch receptors to detect angiogenesis and treat solid tumors
Zhifu Wang, Fan Wang, Junjie Zhong, Tongming Zhu, Yongtao Zheng, Tong Zhao, Qiang Xie, Fukai Ma, Ronggang Li, Qisheng Tang, Feng Xu, Xueying Tian, Jian‐Hong Zhu
Abstract
Angiogenesis is a necessary process for solid tumor growth. Cellular markers for endothelial cell proliferation are potential targets for identifying the vasculature of tumors in homeostasis. Here we customize the behaviors of engineered cells to recognize Apj, a surface marker of the neovascular endothelium, using synthetic Notch (synNotch) receptors. We designed apelin-based synNotch receptors (AsNRs) that can specifically interact with Apj and then stimulate synNotch pathways. Cells engineered with AsNRs have the ability to sense the proliferation of endothelial cells (ECs). Designed for different synNotch pathways, engineered cells express different proteins to respond to angiogenic signals; therefore, angiogenesis can be detected by cells engineered with AsNRs. Furthermore, T cells customized with AsNRs can sense the proliferation of vascular endothelial cells. As solid tumors generally require vascular support, AsNRs are potential tools for the detection and therapy of a variety of solid tumors in adults.