Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy
Fig 7
TME release of payload can drive efficacy in tumor xenografts.
Experimental data from Tsao et al. [11] (top) shows the growth of untreated HER2-negative MDA-MB-468 xenografts injected in the mammary fat pad of SCID mice (control) or treated with three injections of 10 mg/kg T-DXd on days 0, 7, and 14. Experimental data (Experiment A) were collected from a mouse with HER2-positive and HER2-negative dual-implanted tumors and data (Experiment B) were collected from a mouse with only one HER2-negative tumor. In simulations, a cleavage rate constant (kCleave) of 4x10-5/s was able to capture the efficacy in the HER2-negative tumor. Error bars represent standard deviation; each simulation point is the result of 300 simulation runs (100 simulations run in triplicate).