Development and preclinical evaluation of a novel FGFR3-targeted antibody-drug conjugate in bladder cancer - PubMed
12 hours ago
- #Bladder cancer
- #FGFR3
- #Antibody-drug conjugate
- Development of a novel FGFR3-targeted ADC, LZU-WZLYFG001, for bladder cancer treatment.
- Composition includes a humanized anti-FGFR3 IgG1 monoclonal antibody, cleavable GGFG linker, and payload DXD.
- Achieved a drug-to-antibody ratio (DAR) of eight through thiol-based chemistry.
- Demonstrated high purity, targeting specificity, and low endotoxin levels in preclinical assessments.
- Significantly inhibited bladder cancer cell proliferation, migration, and invasion at nanomolar concentrations.
- Efficacy strongly correlated with FGFR3 expression levels.
- Mechanistic studies confirmed binding to FGFR3, internalization, and lysosomal release of the ADC.
- Superior efficacy compared to gemcitabine + cisplatin (GC) regimen, especially in GC-resistant PDX tumors.
- Exhibited robust 3D penetration, bystander effect, and no significant short-term toxicity.
- Potential as a novel therapeutic option for bladder cancer highlighted.