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Chimeric antigen receptor (CAR) T-cell based immunotherapy has shown itspotential in treating blood cancers, and its application to solid tumors iscurrently being extensively investigated. For glioma brain tumors, various CART-cell targets include IL13Ra2, EGFRvIII, HER2, EphA2, GD2, B7-H3, andchlorotoxin. In this work, we are interested in developing a mathematical modelof IL13Ra2 targeting CAR T-cells for treating glioma. We focus on extending thework of Kuznetsov et al. (1994) by considering binding of multiple CAR T-cellsto a single glioma cell, and the dynamics of these multi-cellular conjugates.Our model more accurately describes experimentally observed CAR T-cell killingassay data than a model which does not consider cell binding. Moreover, wederive conditions in the CAR T-cell expansion rate that determines treatmentsuccess or failure. Finally, we show that our model captures distinct CART-cell killing dynamics at low, medium, and high antigen receptor densities inpatient-derived brain tumor cells.

Modeling interaction of Glioma cells and CAR T-cells considering multiple CAR T-cells bindings