8UCD

Cryo-EM structure of human STEAP1 in complex with AMG 509 Fab

Summary for 8UCD

• Entry DOI: 10.2210/pdb8ucd/pdb
• EMDB information: 42124
• Descriptor: Metalloreductase STEAP1, AMG 509 anti-STEAP1 Fab, heavy chain, AMG 509 anti-STEAP1 Fab, light chain, ... (7 entities in total)
• Functional Keywords: membrane protein, antibody, cancer, membrane protein-immune system complex, membrane protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 173750.62

Authors

Li, F.,Bailis, J.M.,Zhang, H. (deposition date: 2023-09-26, release date: 2023-11-22, Last modification date: 2024-11-13)

Primary citation

Nolan-Stevaux, O.,Li, C.,Liang, L.,Zhan, J.,Estrada, J.,Osgood, T.,Li, F.,Zhang, H.,Case, R.,Murawsky, C.M.,Estes, B.,Moore, G.L.,Bernett, M.J.,Muchhal, U.,Desjarlais, J.R.,Staley, B.K.,Stevens, J.,Cooke, K.S.,Aeffner, F.,Thomas, O.,Stieglmaier, J.,Lee, J.L.,Coxon, A.,Bailis, J.M.
AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity against Prostate Cancer.
Cancer Discov, 14:90-103, 2024

PubMed Abstract: The tumor-associated antigen 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 cells that express STEAP1. AMG 509 mediates potent T cell-dependent cytotoxicity of prostate cancer cell lines in vitro and promotes tumor regression in xenograft and syngeneic mouse models of prostate cancer 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 patient with mCRPC who achieved an objective response on AMG 509 treatment.

PubMed: 37861452
DOI: 10.1158/2159-8290.CD-23-0984

Experimental method

ELECTRON MICROSCOPY (3 Å)