GFRA1-PBD

GFRA1-PBD is a preclinical-stage antibody-drug conjugate (ADC) developed by MedImmune (a subsidiary of AstraZeneca) targeting glial cell line-derived neurotrophic factor (GDNF) family receptor alpha-1 (GFRA1). The ADC consists of a humanized anti-GFRA1 monoclonal antibody (clone 10H9) site-specifically conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine (SG3249) via a protease-cleavable linker. GFRA1 is overexpressed in specific breast cancer subsets, particularly estrogen receptor (ER)-positive breast cancers, while showing limited expression in normal tissues. Upon binding to GFRA1, the ADC is rapidly internalized, releasing the PBD dimer payload which acts as a potent DNA alkylating agent, inducing DNA double-strand breaks and subsequent apoptosis. GFRA1-PBD has demonstrated robust anti-tumor activity and bystander cell killing in GFRA1-positive cell lines and patient-derived xenograft (PDX) models of breast cancer.

Other names

GFRA1 targeted antibody-drug conjugate (Medimmune)GFRA1-targeted antibody-drug conjugateGFRA-1-targeted antibody-drug conjugateGFRA 1-targeted antibody-drug conjugate