INVESTIGATING THE IMPACT OF PHARMACOKINETIC VARIABILITY ON THE EFFICACY OF BISPECIFIC T-CELL ENGAGERS (BITES) IN CANCER TREATMENT: A PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODELING APPROACH

Abstract

Bispecific T-cell Engagers (BiTEs) are a promising cancer treatment, but their efficacy is influenced by pharmacokinetic variability. This study employed a novel PBPK model to investigate the impact of pharmacokinetic variability on the efficacy of Bispecific T-cell Engagers (BiTEs) in cancer treatment. The model incorporated tumor growth, drug distribution, and cytotoxicity, with parameters estimated from literature and experimental data. The model simulated the spatial and temporal dynamics of tumor cell growth and treatment response, revealing a significant reduction in tumor size (97.6% decrease from initial volume) and a corresponding increase in cytotoxicity effect (initial cytotoxicity effect of 1e244, decreasing to -7 by day 8). The results showed that pharmacokinetic variability significantly influences BiTE efficacy, with drug concentrations varying across compartments (tumor, blood, liver, kidney, and fat) and peaking at different times (Tmax = 6 days). This study demonstrates the significant impact of pharmacokinetic variability on BiTE efficacy, highlighting the importance of optimizing drug dosing strategies and developing novel drug designs that sustain cytotoxicity over extended periods. The findings suggest that personalized treatment regimens and optimized drug dosing strategies could lead to improved treatment outcomes, highlighting the importance of considering pharmacokinetic variability in cancer treatment.