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

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 c...

Full description

Saved in:
Bibliographic Details
Published inarXiv.org
Main Authors Li, Runpeng, Sahoo, Prativa, Wang, Dongrui, Wang, Qixuan, Brown, Christine E, Rockne, Russell C, Cho, Heyrim
Format Paper
LanguageEnglish
Published Ithaca Cornell University Library, arXiv.org 18.01.2022
Subjects
Antigens
Binding
Brain
Brain cancer
Mathematical models
Receptors
Tumors
Online AccessGet full text

Cover

More Information
Summary: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.
ISSN:2331-8422