Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy
Fig 5
Treating nude vs. syngeneic mice with T-DXd.
(A) Using the CT26 nude mice growth rates previously calibrated from Rios-Doria et al. [8], we simulated T-DXd with a 20-fold decrease in potency (to account for the differences in sensitivity between human NCI-N87 cancer cells and mouse CT26 cancer cells) and find agreement with the experimental data showing little efficacy in mouse cancer cells grown in the nude mouse model. (B) Using the growth rates from the syngeneic mouse model, we simulated T-DXd treatment and find a similar efficacy to the experimental data. We also simulated the impact of activated T cell killing alone (no payload efficacy) and see similar tumor volumes, indicating that efficacy is mainly driven by T cell activation in this model. Error bars represent standard deviation; each simulation point is the result of 300 simulation runs (100 simulations run in triplicate).