Fig. 2.

Schematic illustration of the cell-level PK/PD model for analyzing the inhibitory effect on receptor activation of anti-EGFR antibodies. a Cell-level receptor model of receptor activation and inhibition. The cellular model describes the transient inhibitory effect of a therapeutic antibody by competitively binding the targeted receptor and thereby decreasing the active ligand-receptor complexes. b Cell-level PK/PD model used to study the trajectory of the drug concentration and the impact of biophysical properties of anti-EGFR antibodies. c Three different transient measures of the reduction in the number of active receptors: the integral, the peak, and the duration of inhibition. d Extended cell-level PK/PD model including tumor cells with elevated EGFR levels due to alteration of receptor dynamics used to compare the inhibitory effect of therapeutic antibodies on tumor cells and normal cells to optimize tumor specificity