AMG 509 (Xaluritamig)，一种抗 STEAP1 XmAb 2 1 T 细胞重定向免疫疗法，具有亲和力依赖性抗前列腺癌活性。
AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity Against Prostate Cancer.
发表日期：2023 Oct 20
作者：
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
来源：
Cancer Discovery
摘要：
肿瘤相关抗原前列腺六跨膜上皮抗原 1 (STEAP1) 是一个潜在的治疗靶点，在大多数前列腺肿瘤中表达，并且在转移性去势抵抗性前列腺癌 (mCRPC) 中表达水平升高。我们开发了一种针对 STEAP1 的 XmAb 2 1 T 细胞接合器 (TCE) 分子 AMG 509（也称为 xaluritamig），旨在重定向 T 细胞以杀死表达 STEAP1 的前列腺癌 (PCa) 细胞。 AMG 509 在体外介导 PCa 细胞系的强效 T 细胞依赖性细胞毒性，并在体内促进 PCa 异种移植和同基因小鼠模型中的肿瘤消退。与正常细胞相比，AMG 509 的亲合力驱动活性能够选择性地选择性地筛选具有高 STEAP1 表达的肿瘤细胞。 AMG 509 是第一个进入临床测试的 STEAP1 TCE，我们报告了一名 mCRPC 患者的案例研究，该患者对 AMG 509 治疗取得了客观缓解。
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.