Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy
Fig 12
Efficacy of combined mechanisms alongside targeted delivery to moderate and high HER2-expressing tumors.
(TD = targeted delivery, ICadd = immune cell additive activity, ICsyn = immune cell synergistic activity, SYSrel = systemic release, MACrel = mac release, TMErel = TME release) The addition of systemic release to TME release was enough to regress tumors. The addition of either systemic release or TME release to mac release was enough to drive further tumor regression. For comparison with the combined target-independent mechanisms, tumors with moderate HER2 expression (100,000 HER2/cell) and high HER2 expression (1,000,000 HER2/cell) underwent simulated treatment, and both resulted in very strong efficacy, consistent with the high efficiency of targeted payload delivery. Error bars represent standard deviation; each bar is the result of 300 simulation runs (100 simulations run in triplicate). The dotted line is the cutoff for 1000 mm3, in which tumor volumes below 1000 mm3 achieve regression.