8ucd
From Proteopedia
Cryo-EM structure of human STEAP1 in complex with AMG 509 Fab
Structural highlights
FunctionSTEA1_HUMAN Metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+). Uses NAD(+) as acceptor.[UniProtKB:Q9CWR7] Publication Abstract from PubMedThe tumor-associated antigen Six-Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is a potential therapeutic target that is expressed in most prostate tumors and at increased levels in metastatic castration-resistant prostate cancer (mCRPC). We developed a STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), that is designed to redirect T cells to kill prostate cancer (PCa) cells that express STEAP1. AMG 509 mediates potent T cell-dependent cytotoxicity of PCa cell lines in vitro, and promotes tumor regression in xenograft and syngeneic mouse models of PCa in vivo. The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a mCRPC patient who achieved an objective response on AMG 509 treatment. AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity Against Prostate Cancer.,Nolan-Stevaux O, Li C, Liang L, Zhan J, Estrada J, Osgood T, Li F, Zhang H, Case R, Murawsky CM, Estes B, Moore GL, Bernett MJ, Muchhal U, Desjarlais JR, Staley BK, Stevens J, Cooke KS, Aeffner F, Thomas O, Stieglmaier J, Lee JL, Coxon A, Bailis JM Cancer Discov. 2023 Oct 20. doi: 10.1158/2159-8290.CD-23-0984. PMID:37861452[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
