Tuning the specificity of a Two-in-One Fab against three angiogenic antigens by fully utilizing the information of deep mutational scanning.

ABSTRACT: Monoclonal antibodies developed for therapeutic or diagnostic purposes need to demonstrate highly defined binding specificity profiles. Engineering of an antibody to enhance or reduce binding to related antigens is often needed to achieve the desired biologic activity without safety concern. Here, we describe a deep sequencing-aided engineering strategy to fine-tune the specificity of an angiopoietin-2 (Ang2)/vascular endothelial growth factor (VEGF) dual action Fab, 5A12.1 for the treatment of age-related macular degeneration. This antibody utilizes overlapping complementarity-determining region (CDR) sites for dual Ang2/VEGF interaction with K_D in the sub-nanomolar range. However, it also exhibits significant (K_D of 4 nM) binding to angiopoietin-1, which has high se

SUBMITTER: Koenig P 

PROVIDER: S-EPMC5540083 | biostudies-literature | 2017 Aug/Sep

REPOSITORIES: biostudies-literature