Lei Wang, Yufeng Xiao, Yuewan Luo, Rohan P Master, Jiao Mo, Myung-Chul Kim, Yi Liu, Chandra K Maharjan, Urvi M Patel, Umasankar De, Madison E Carelock, Tanzia Islam Tithi, Xiangming Li, Donald R Shaffer, Kevin R Guertin, Haoyang Zhuang, Emily Moser, Keiran S M Smalley, Dongwen Lv, Daohong Zhou, Guangrong Zheng, Weizhou Zhang
An effective cancer therapy requires killing cancer cells and targeting the tumor microenvironment (TME). Searching for molecules critical for multiple cell types in the TME, we identified NR4A1 as one such molecule that can maintain the immune suppressive TME. Here, we establish NR4A1 as a valid target for cancer immunotherapy and describe a first-of-its-kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 degrades NR4A1 within hours in vitro and exhibits long-lasting NR4A1 degradation in tumors with an excellent safety profile...
March 4, 2024: Journal of Experimental Medicine