The 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.
Cancer discovery. 2023 Oct 20 [Epub ahead of print]
Olivier Nolan-Stevaux, Cong Li, Lingming Liang, Jinghui Zhan, Juan Estrada, Tao Osgood, Fei Li, Hanzhi Zhang, Ryan Case, Christopher M Murawsky, Bram Estes, Gregory L Moore, Matthew J Bernett, Umesh Muchhal, John R Desjarlais, Binnaz K Staley, Jennitte Stevens, Keegan S Cooke, Famke Aeffner, Oliver Thomas, Julia Stieglmaier, Jae-Lyun Lee, Angela Coxon, Julie M Bailis
Gilead Sciences (United States), Foster City, United States., Amgen Inc, South San Francisco, CA, United States., Amgen Inc, south san francisco, ca, United States., Amgen Inc., Thousand Oaks, CA, United States., Amgen (United States), South San Francisco, CA, United States., Amgen (United States), United States., Amgen Inc., South San Francisco, CA, United States., Amgen Inc., Burnaby, British Columbia, Canada., Xencor (United States), Pasadena, CA, United States., IGM Biosciences (United States), United States., Amgen (United States), Thousand Oaks, CA, United States., Amgen Research (Munich) GmbH, München, Bayern, Germany., Amgen Research (Munich) GmbH, Munich, Germany., Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (South), Republic of.