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

TL;DR

This paper develops a mathematical model for CAR T-cell therapy targeting glioma, incorporating multiple CAR T-cell bindings to tumor cells, and analyzes how binding dynamics influence treatment success.

Contribution

It extends existing models by including multi-cellular conjugates and derives conditions for treatment success based on CAR T-cell expansion rates.

Findings

Model fits experimental CAR T-cell killing data more accurately

Identifies conditions for treatment success or failure

Captures different killing dynamics at varying antigen densities

Abstract

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