Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy
Fig 10
Predicted efficacy in HER2 low (10,000 HER2/cell) tumors in humans and cell killing mechanisms.
Simulations tested control (no treatment), targeted delivery (5.4 mg/kg T-DXd only), baseline T cell killing only, and additive (baseline T cell killing plus targeted delivery) and synergistic (activated T cell killing plus targeted delivery) mechanisms. (A) With 10K HER2/cell, tumor growth is slowed but does not regress with targeted delivery of T-DXd alone. Infiltrating T cells without treatment also slow growth but don’t regress the tumor. However, a combination of 5.4 mg/kg of T-DXd with infiltrating T cells (baseline T cell killing) can regress the tumor, and activation of the T cells (synergy) can drive a strong response. (B) The first 2000 cells killed by each treatment regimen are plotted over time. Cells killed due to direct action of DXd (targeted delivery) vs T cell killing are plotted to separately to show their relative contributions. Compared to T-DXd treatment alone, the presence of T cells reduces the number of cancer cells killed by the drug with a further reduction following activation due to competing mechanisms. The T cell killing rate is not impacted as strongly by the T-DXd treatment, but it is substantially enhanced through activation. Error bars represent standard deviation; each simulation point is the result of 300 simulation runs (100 simulations run in triplicate).