Amina Eladdadi | Searcharxiv

arXiv2026

A Predictive Model for Synergistic Oncolytic Virotherapy: Unveiling the Ping-Pong Mechanism and Optimal Timing of Combined Vesicular Stomatitis and Vaccinia Viruses

We present a mathematical model that describes the synergistic mechanism of combined Vesicular Stomatitis Virus (VSV) and Vaccinia Virus (VV). The model captures the dynamic interplay between tumor cells, viral replication, and the interferon-mediated immune response, revealing a `ping-pong' synergy where VV-infected cells produce B18R protein that neutralizes interferon-$\alpha$, thereby enhancing VSV replication within the tumor. Numerical simulations demonstrate that this combination achieves complete tumor clearance in approximately 50 days, representing an 11\% acceleration compared to VV monotherapy (56 days), while VSV alone fails to eradicate tumors. Through bifurcation analysis, we identify critical thresholds for viral burst size and B18R inhibition, while sensitivity analysis highlights infection rates and burst sizes as the most influential parameters for treatment efficacy. Temporal optimization reveals that therapeutic outcomes are maximized through immediate VSV administration followed by delayed VV injection within a 1-19 day window, offering a strategic approach to overcome the timing and dosing challenges inherent in OVT.

q-bio.QM↗

arXiv2018

Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis

Oncolytic virotherapy (OV) has been emerging as a promising novel cancer treatment that may be further combined with the existing therapeutic modalities to enhance their effects. To investigate how OV could enhance chemotherapy, we propose an ODE based model describing the interactions between tumour cells, the immune response, and a treatment combination with chemotherapy and oncolytic viruses. Stability analysis of the model with constant chemotherapy treatment rates shows that without any form of treatment, a tumour would grow to its maximum size. It also demonstrates that chemotherapy alone is capable of clearing tumour cells provided that the drug efficacy is greater than the intrinsic tumour growth rate. Furthermore, OV alone may not be able to clear tumour cells from body tissue but would rather enhance chemotherapy if viruses with high viral potency are used. To assess the combined effect of OV and chemotherapy we use the forward sensitivity index to perform a sensitivity analysis, with respect to chemotherapy key parameters, of the virus basic reproductive number and the tumour endemic equilibrium. The results from this sensitivity analysis indicate the existence of a critical dose of chemotherapy above which no further significant reduction in the tumour population can be observed. Numerical simulations show that a successful combinational therapy of the chemotherapeutic drugs and viruses depends mostly on the virus burst size, infection rate, and the amount of drugs supplied. Optimal control analysis was performed, by means of Pontryagin's principle, to further refine predictions of the model with constant treatment rates by accounting for the treatment costs and sides effects.

math.OC↗