Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy
Fig 9
Minimum threshold of HER2 expression in mice and humans for efficacy of targeted delivery alone.
The growth rates of tumors with varying low expression levels were simulated in SimADC following treatment with 5.4 mg/kg of T-DXd. Using tumor regression (below starting volume, as defined by the horizontal dashed line) at 21 days (defined by the vertical dashed line) as the threshold for efficacy, (A) 50,000 HER2/cell were needed in mice while (B) 30,000 HER2/cell were sufficient in the human simulations. The difference occurs from scaling the pharmacokinetic parameters from mice to humans. Error bars represent standard deviation; each simulation point is the result of 300 simulation runs (100 simulations run in triplicate).