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Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer
Leticia R Paiva1, Hallan S Silva, Silvio C Ferreira
1Departamento de Física, Universidade Federal de Viçosa, 36570-000 Viçosa, MG, Brazil.
Abstract:
Oncolytic virotherapy-the use of viruses that specifically kill tumor cells-is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8(+) T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.
Insights
Oncolytic virotherapy uses viruses to kill cancer cells but is hindered by immune responses. Mathematical modeling shows reprogramming the tumor immune microenvironment can enhance treatment effectiveness in patients.
Area of Science:
- Oncology
- Immunology
- Mathematical Biology
Background:
- Oncolytic virotherapy, using viruses to selectively destroy tumor cells, shows promise for cancer treatment.
- Therapeutic efficacy is often limited by the host's immune response to the viral infection.
- Understanding immune interference is crucial for optimizing virotherapy outcomes.
Purpose of the Study:
- To develop a multiscale mathematical model to investigate immune system interference with oncolytic virotherapy.
- To identify mechanisms by which immune responses impact viral oncolytic activity.
- To explore strategies for enhancing oncolytic virotherapy in immune-competent hosts.
Main Methods:
- Development of a multiscale mathematical model incorporating cytotoxic T cells, infected cancer cells, and immune clearance mechanisms.
- Simulations to analyze the interplay between viral oncolysis and host immune components.
- Modeling of virus inactivation by antibodies and innate immune clearance.
Main Results:
- The immune microenvironment significantly impacts oncolytic virotherapy outcomes.
- Reprogramming the tumor immune microenvironment can substantially enhance treatment in immune-competent hosts.
- Strategies include impairing CD8(+) T cell motility or blocking lymphocyte recruitment.
Conclusions:
- Mathematical modeling provides insights into optimizing oncolytic virotherapy.
- Targeting immune responses, such as CD8(+) T cell motility and lymphocyte recruitment, can improve treatment efficacy.
- Theoretical findings may guide the design of novel viral vectors and clinical protocols.
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