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Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy

Fig 2

Hybrid Agent-Based Model (SimADC) Combines Drug Gradients with Cellular Agents.

(A) A grid of thousands of cells incorporates blood vessels (source and sink of ADCs and payloads from the plasma), cancer cells that divide or die with probabilities based on local conditions, T cells for immune cell killing, and macrophages for Fc-mediated payload release. (B) The grid is overlayed with drug gradients (including bound and unbound ADC and free payload in the intracellular and extracellular space) that are used to capture bystander killing and determine the probability of cell death. (C) The updated model incorporates targeted delivery (inclusive of bystander effects) as in our previous models but also adds T cell killing (baseline and activated), macrophage-mediated payload release (mac release), extracellular ADC linker cleavage (TME release), and uptake of free payload from the plasma (systemic release). Created in BioRender. Calopiz, M. (2026) https://BioRender.com/doavg9f and https://BioRender.com/a2tocth.

Fig 2

doi: https://doi.org/10.1371/journal.pcbi.1013872.g002