Abstract
Background/aim
Carcinoembryonic antigen (CEA) contributes to colorectal cancer surveillance and has been implicated in colorectal liver metastasis through interaction with the hepatic carcinoembryonic antigen receptor (CEAR). Because direct experimental estimation of CEA-CEAR binding characteristics remains technically challenging, computational modelling may help identify biologically plausible receptor-occupancy parameters for anti-CEA monoclonal antibody (MAb) development.Materials and methods
A stochastic ligand-receptor occupancy model was developed to simulate CEA, CEAR and anti-CEA MAb interactions across repeated virtual cohorts. Parameter sweeps evaluated combinations of CEAR occupancy threshold, CEA-CEAR interaction strength and MAb-CEA interaction strength associated with reduced simulated hepatic colonization. Statistically significant parameter combinations (pResults
An exhaustive grid search of 9,261 parameter combinations identified 6,250 retained parameter combinations meeting the predefined screening criterion (pConclusion
This study proposes a receptor-occupancy framework for CEA-mediated hepatic metastasis and provides computationally derived parameter ranges that may assist experimental optimization of anti-CEA MAbs.