Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy
Fig 6
Fc receptor-mediated internalization of ADCs can drive high efficacy in macrophage-dense tumors.
Our macrophage model pharmacokinetic and pharmacodynamic parameters were calibrated to literature experimental data from Li et al. [10], who measured (A) intratumoral free payload concentrations and (B) efficacy in tumors with high macrophage infiltration (~50% macrophages in the tumor) after dosing a targeted (CD30 receptor binding) and a non-targeted (IgG, mainly binding to Fc receptors on macrophages) ADC with an MMAE payload. Our simulations show similar concentrations of intratumoral payload, also resulting in similar efficacy with both types of ADCs after model calibration. Error bars represent standard deviation; each simulation point is the result of 300 simulation runs (100 simulations run in triplicate).