Michael J McPherson, Adrian D Hobson, Axel Hernandez, Christopher C Marvin, Wendy Waegell, Christian Goess, Jason Z Oh, Dan Shi, Martin E Hayes, Lu Wang, Lu Wang, Diana Schmidt, Zhi Wang, Victoria Pitney, Kimberley McCarthy, Ying Jia, Ce Wang, Bit Na Kang, Shaughn Bryant, Suzanne Mathieu, Melanie Ruzek, Julie Parmentier, Ronilda R D'Cunha, Yinuo Pang, Lucy Phillips, Nathan J Brown, Jianwen Xu, Candace Graff, Yu Tian, Kenton L Longenecker, Wei Qiu, Haizhong Zhu, Wei Liu, Pingping Zheng, Yingtao Bi, Robert Stoffel
Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti-tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity...
March 20, 2024: Science Translational Medicine