European Conference on Mathematical and Theoretical Biology (ECMTB 2026)

A Minimal Model Framework for Robust CAR-T Cell and Oncolytic Virus Combination Therapy

MS134-01

15 Jul 2026, 11:10

20m

15.03 - HS (University of Graz)

Minisymposium Talk Mathematical Epidemiology Novel Data Streams for Disease Modeling: Challenges and Opportunities

Speaker

Aisha Tursynkozha (Astana IT University)

Description

Glioblastoma remains one of the most lethal brain cancers. Combination therapy using CAR-T cells and oncolytic viruses shows promise, yet the mechanisms underlying their synergy remain poorly understood. We develop mathematical models to analyze IL-13Rα2-targeting CAR-T cells and the oncolytic virus C134 using patient-derived glioblastoma data. We propose a minimal model framework for predicting outcomes of combination immunotherapy. By applying timescale separation between rapid viral dynamics and slower cellular processes, we derive quasi-steady-state (QSS) approximations that reduce model complexity while maintaining predictive accuracy. The QSS model contains nine parameters compared with eleven in the full model and achieves comparable fits to the data. Model comparisons using the Akaike Information Criterion indicate that the QSS model is generally favored, particularly for oncolytic virus monotherapy and several combination therapy conditions. These results demonstrate that simplified QSS formulations effectively capture viral dynamics and provide a practical framework for analyzing and optimizing combination immunotherapies.

Bibliography

@article{pell2025dynamic,

title={Dynamic PD-L1 regulation shapes tumor immune escape and response to immunotherapy},

author={Pell, Bruce and Kalizhanova, Aigerim and Tursynkozha, Aisha and Dengi, Denise and Kashkynbayev, Ardak and Kuang, Yang},

journal={Cancers},

volume={17},

number={23},

pages={3803},

year={2025}

}

@article{conte2025car,

title={CAR T-cell and oncolytic virus dynamics and determinants of combination therapy success for glioblastoma},

author={Conte, Martina and Xella, Agata and Woodall, Ryan T and Cassady, Kevin A and Branciamore, Sergio and Brown, Christine E and Rockne, Russell C},

journal={Mathematical Biosciences},

pages={109531},

year={2025}

}

@article{mahasa2022combination,

title={A combination therapy of oncolytic viruses and chimeric antigen receptor T cells: a mathematical model proof-of-concept},

author={Mahasa, Khaphetsi Joseph and Ouifki, Rachid and Eladdadi, Amina and de Pillis, Lisette},

journal={Mathematical Biosciences and Engineering},

volume={19},

number={5},

pages={4429--4457},

year={2022}

}