Anticancer research · 2026
Computational Modelling of CEA-CEAR Receptor Occupancy for Anti-CEA Therapy in Colorectal Liver Metastasis.
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Cristaudo Adam Thomas, Morris David Lawson
Аннотация
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 (p<0.05) were retained for summary analysis.
RESULTS: An exhaustive grid search of 9,261 parameter combinations identified 6,250 retained parameter combinations meeting the predefined screening criterion (p<0.05). Median and interquartile range values were 0.65 (0.40-0.90) for CEAR occupancy threshold, 0.50 (0.23-0.78) for MAb-CEA interaction strength and 0.65 (0.35-0.95) for CEA-CEAR interaction strength. These findings define a biologically plausible receptor-occupancy landscape associated with reduced simulated hepatic colonization rather than a single optimal affinity. Approximate nanomolar conversions were explored solely to guide future experimental assay design.
CONCLUSION: 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.
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 (p<0.05) were retained for summary analysis.
RESULTS: An exhaustive grid search of 9,261 parameter combinations identified 6,250 retained parameter combinations meeting the predefined screening criterion (p<0.05). Median and interquartile range values were 0.65 (0.40-0.90) for CEAR occupancy threshold, 0.50 (0.23-0.78) for MAb-CEA interaction strength and 0.65 (0.35-0.95) for CEA-CEAR interaction strength. These findings define a biologically plausible receptor-occupancy landscape associated with reduced simulated hepatic colonization rather than a single optimal affinity. Approximate nanomolar conversions were explored solely to guide future experimental assay design.
CONCLUSION: 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.