Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy
Fig 8
SimADC predicts responses to systemic DXd in mouse xenografts.
(A) The plasma clearance parameters for free DXd were fit to experimental data from Okamoto et al. [26] following intravenous delivery. We simulated a dose of 0.04 mg/kg (vs. 1 mg/kg used in the experiment) to match the initial concentration. (B) Our previously-calibrated DXd parameter set was validated by comparison to experimental data from Kumazawa et al. [27] (left) after calibrating our cell doubling time parameters to the control curve measured from human SC-6 xenografts in nude mice. We doubled our maximum probability of cell killing to adjust for the change in potency (0.045 for DXd vs. 0.09 for exatecan) and dosed a total of 2 mg/kg (vs. a total of 50 mg/kg used in the experiment) based on our equivalent model dose from (A). We simulated the following dosing regimens as outlined in Kumazawa et al. Each color corresponds to the dosing strategy for each curve, and the arrows represent the dosing schedule for each experiment and simulation run: (i, green) q4d x 3, (ii, red) q4d x 4, and (iii, blue) q7d x 3. Error bars represent standard deviation; each simulation point is the result of 300 simulation runs (100 simulations run in triplicate).