Fig. 7
From: Ab locks for improving the selectivity and safety of antibody drugs
Cross-masking antibodies for limiting off-target effects of Ab drugs. Donaldson et al. used a cross-masking Ab approach to simultaneously block two Ab drugs. In this design, one Ab drug was linked with a corresponding antigen epitope (e.g., mutated soluble EGFR domain III (sEGFRdIII)) of another Ab drug via a protease-specific substrate peptide (VPLSLYS for MMP-9) and vice versa. The mutated masking epitope can significantly reduce the binding affinity of the linked Ab drug to a specific antigen and increase the releasing efficiency from the cross-masking Ab after MMP-9 cleavage, thereby restoring the antigen-neutralizing activity of the Ab drug. Ab, antibody; EGFR, epidermal growth factor receptor; MMP, matrix metalloproteinase