Harnessing the Power of AMG 509: Targeting STEAP1-Expressing Cancers with a Novel Bispecific T Cell-Recruiting Antibody

3 June 2024
AMG 509 is a pioneering STEAP1 x CD3 bispecific antibody developed to target STEAP1, a cell surface antigen significantly expressed in prostate cancer and Ewing sarcoma (EWS). This novel therapy is designed to bridge T cells to cancer cells, prompting an immune response. AMG 509 is equipped with two anti-STEAP1 Fab domains for cancer cell binding, an anti-CD3 scFv domain for T cell binding, and an engineered Fc domain to enhance serum half-life and eliminate effector function.

The study revealed that STEAP1 is predominantly absent in normal tissues except the prostate epithelium and some lung macrophages but is present in the majority of primary and metastatic prostate cancer tissues, as well as bone metastases and EWS cell lines and xenograft models. AMG 509 demonstrated high affinity for both human and cynomolgus monkey CD3 and STEAP1-expressing cells. It induced potent T cell-mediated lysis of STEAP1-positive cancer cells with remarkable potency, being significantly more effective than a comparable molecule with a single anti-STEAP1 Fab domain.

The antibody also displayed T cell engagement characteristics, such as proliferation and cytokine release, and triggered robust anti-tumor activity and CD8+ T cell activation in vivo in prostate cancer and EWS models. Nonclinical safety studies in cynomolgus monkeys indicated that AMG 509 can be safely administered at potentially clinically effective doses.

In summary, AMG 509 is a first-in-class T cell-recruiting antibody with a potent and specific mechanism for targeting STEAP1-positive cancers. It is currently under evaluation in a phase 1 clinical trial for patients with metastatic castration-resistant prostate cancer (mCRPC).

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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Click on the image below to go directly to the Translational Medicine search interface.

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