Biophysical cartography of the native and human-engineered antibody landscapes quantifies the plasticity of antibody developability.

ABSTRACT: Designing effective monoclonal antibody (mAb) therapeutics faces a multi-parameter optimization challenge known as "developability", which reflects an antibody's ability to progress through development stages based on its physicochemical properties. While natural antibodies may provide valuable guidance for mAb selection, we lack a comprehensive understanding of natural developability parameter (DP) plasticity (redundancy, predictability, sensitivity) and how the DP landscapes of human-engineered and natural antibodies relate to one another. These gaps hinder fundamental developability profile cartography. To chart natural and engineered DP landscapes, we computed 40 sequence- and 46 structure-based DPs of over two million native and human-engineered single-chain antibody sequences. We fin

SUBMITTER: Bashour H 

PROVIDER: S-EPMC11291509 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature