Assessing Histologic Biomarkers of Response to Micvotabart Pelidotin (MICVO), the First-in-Class ADC Targeting the Tumor Extracellular Matrix Protein Extradomain-B of Fibronectin
- MICVO binds to extradomain-B of fibronectin (EDB+FN) in the tumor extracellular matrix where the linker is cleaved by extracellular cathepsins to allow free auristatin payload to diffuse into and kill cancer cells directly, via the bystander effect, and by eliciting immunogenic cell
- Pyxis Oncology developed an exploratory immunohistochemistry assay and scoring system to measure the intensity and distribution of EDB+FN in the extracellular matrix of the tumor stroma of preclinical and clinical samples
- Biological drivers, in addition to EDB+FN target expression, may confer sensitivity to MICVO, suggesting a multi factorial biomarker approach to understanding tumor responsiveness to treatment