Fig. 6
From: Ab locks for improving the selectivity and safety of antibody drugs
Affinity peptide-based Ab lock for masking the antigen binding activity of Ab drugs. CytomX therapeutics, Inc. developed PROBODY therapeutics by masking the antigen binding site of Ab drugs (e.g., anti-EGFR Ab, anti-VCAM-1 Ab or anti-EGFR ADC) with an affinity peptide screened out from phage display library technology and linked it to an Ab through a protease substrate peptide (e.g., LSGRSDNH for uPA and MT-SP1). The Pro-Ab exhibits weaker antigen binding ability than the original Ab drug, maintains intact format in systemic circulation and the biological activity could be specifically restored in the tumor microenvironment in a protease dependent manner. Ab, antibody; EGFR, epidermal growth factor receptor; ADC, antibody-drug conjugate; VCAM-1, vascular cell adhesion molecule 1; uPA, urokinase plasminogen activator; MT-SP1, activated membrane type-serine protease 1