Antibodies to Modulate Surface Receptor Systems Are Often Bivalent and Must Compete in a Two‐Dimensional Cell Contact Region

Mechanistic models have been developed to calibrate to and predict pharmacodynamic (PD) responses for therapeutic antibodies that modulate cell surface molecules. In order to accurately reflect in-vivo antibody-receptor interactions, and predict receptor occupancy and proximal PD, a thorough accounting of biophysical principals for bivalent antibodies and surface-constrained receptor-ligand systems needs to be incorporated. We provide salient biophysical considerations for cell surface receptor-ligand interactions, including immune checkpoints, which necessitate model-guided, quantitative analysis of experimental results.