A Mathematical Model for On-Target Off-Tumor Effect of CAR-T Cells on Gliomas

CAR-T cell immunotherapy involves genetically reprogrammed T-lymphocytes that interact with cancer cells and activate an anti-tumor immune response. This therapy has been approved for clinical use hematological cancers, but new challenges have emerged in the treatment of solid tumors. Some include heterogeneity antigen expression found tumors, including antigen-positive non-tumoral cells, inhibitory molecule expression, trafficking difficulty within tumor microenvironment. We proposed a mathematical model to describe “on-target” “off-tumor” effects on gliomas, we investigated which parameters influenced final outcome using global sensitivity analysis. Our highlights dynamics therapy, tumor, healthy populations (antigen-positive glia, antigen-negative neurons), it provides novel insight into consequences effects, particularly neuronal loss.