Fig. 5.

The mechanism underlying increased receptor levels influences tumor specificity of mAbs. a Predicted transient inhibition based on the extended cell-level pharmacokinetic model shown in Fig. 2d for normal cells, tumor cells with a 10-fold increased receptor expression, and tumor cells with a 10-fold decreased internalization of the free and bound receptor. Profiles are shown for the 20 mg/kg (solid line) and 2 mg/kg (dashed line) dose. Both scenarios show similar steady-state activation levels of the receptor, but their response to drug treatment is substantially different. b Antibody specificity as defined in Eq. 29. Cells with a decreased receptor internalization have a much longer duration of inhibition and therefore a higher integral of inhibition than tumor cells with an increased receptor expression