Chimeric Antigen Receptor T cell (CAR T cell) therapy has shown remarkable success in hematological malignancies but limited efficacy against solid tumors due to challenges like antigen heterogeneity and poor infiltration. This study develops a mathematical model of CAR T cell therapy for solid tumors, considering antigen heterogeneity and bystander effects (antigen spreading). Using in vivo data, the model simulates virtual patients to understand bystander killing and explore strategies for enhancement. Results suggest that increasing CAR T cell dosage alone is insufficient; enhancing bystander cell cytotoxicity significantly improves outcomes.

Erdi Kara, Trachette L. Jackson, Chartese Jones, Rockford Sison, Reginald L. McGee II