Related Experiment Video
Updated: Feb 22, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Oncolytic potency and reduced virus tumor-specificity in oncolytic virotherapy. A mathematical modelling approach
Khaphetsi Joseph Mahasa1, Amina Eladdadi2, Lisette de Pillis3
1DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa.
Abstract:
In the present paper, we address by means of mathematical modeling the following main question: How can oncolytic virus infection of some normal cells in the vicinity of tumor cells enhance oncolytic virotherapy? We formulate a mathematical model describing the interactions between the oncolytic virus, the tumor cells, the normal cells, and the antitumoral and antiviral immune responses. The model consists of a system of delay differential equations with one (discrete) delay. We derive the model's basic reproductive number within tumor and normal cell populations and use their ratio as a metric for virus tumor-specificity. Numerical simulations are performed for different values of the basic reproduction numbers and their ratios to investigate potential trade-offs between tumor reduction and normal cells losses. A fundamental feature unravelled by the model simulations is its great sensitivity to parameters that account for most variation in the early or late stages of oncolytic virotherapy. From a clinical point of view, our findings indicate that designing an oncolytic virus that is not 100% tumor-specific can increase virus particles, which in turn, can further infect tumor cells. Moreover, our findings indicate that when infected tissues can be regenerated, oncolytic viral infection of normal cells could improve cancer treatment.
Insights
Mathematical modeling suggests that oncolytic viruses not solely targeting tumor cells may enhance virotherapy. Infecting some normal cells can boost virus replication, potentially improving cancer treatment outcomes when tissue regeneration occurs.
Area of Science:
- Mathematical Biology
- Oncolytic Virotherapy
- Cancer Research
Background:
- Oncolytic virotherapy uses viruses to selectively infect and destroy tumor cells.
- Understanding virus-host interactions is crucial for optimizing treatment efficacy.
- The role of normal cell infection in oncolytic virotherapy remains an area for investigation.
Purpose of the Study:
- To investigate how oncolytic virus infection of normal cells can enhance oncolytic virotherapy.
- To develop a mathematical model to analyze virus-tumor-normal cell dynamics.
- To explore the impact of virus tumor-specificity on treatment outcomes.
Main Methods:
- Formulation of a mathematical model using delay differential equations.
- Derivation of basic reproductive numbers for tumor and normal cell populations.
- Numerical simulations to assess parameter sensitivity and trade-offs.
Main Results:
- Virus tumor-specificity, measured by the ratio of reproductive numbers, influences treatment.
- Model simulations show high sensitivity to parameters affecting early/late therapy stages.
- Non-100% tumor-specific viruses can increase viral load for enhanced tumor cell infection.
Conclusions:
- Designing oncolytic viruses with partial normal cell infectivity may improve therapeutic outcomes.
- Tissue regeneration capacity is a key factor when considering normal cell infection.
- Mathematical modeling provides insights into optimizing oncolytic virotherapy strategies.
Related Concept Videos
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
01:27Tumor Immunotherapy
01:27Pharmacodynamic Models: Overview