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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Adaptive Immunity Determines the Cancer Treatment Outcome of Oncolytic Virus and Anti-PD-1
Kang-Ling Liao1, Kenton D Watt2
1Department of Mathematics, University of Manitoba, 340 UMSU University Centre, Winnipeg, MB, R3T 2N2, Canada. Kang-Ling.Liao@umanitoba.ca.
Abstract:
The immune checkpoint inhibitor, anti-programmed death protein-1 (anti-PD-1), enhances adaptive immunity to kill tumor cells, and the oncolytic virus (OV) triggers innate immunity to clear the infected tumor cells. We create a mathematical model to investigate how the interaction between adaptive and innate immunities under OV and anti-PD-1 affects tumor reduction. For different immunity strength, we create the corresponding virtual baseline patients and cohort patients to decipher the major factors determining the treatment outcome. Global sensitivity analysis indicates that adaptive immunity has more control on the treatment outcome than innate immunity, and whether anti-PD-1 cancels out the OV treatment efficacy depends on the OV dosage and the balance between clearance of infected tumor cells and OV by T cells. The optimal OV infection rate and dosage suggest that OV treatment is more sensitive to adaptive immunity than innate immunity. Our model prediction also indicates that tumor reduction is more sensitive to anti-PD-1 efficacy as adaptive immunity becomes stronger, and anti-PD-1 trends to cancel out the OV treatment efficacy as innate immunity becomes stronger. Based on these results, the recommended treatment protocol for patients with different immunity strength can be determined.
Insights
Anti-programmed death protein-1 (anti-PD-1) and oncolytic viruses (OV) boost immune responses against tumors. Adaptive immunity is key, but treatment efficacy depends on OV dosage and immune cell balance.
Area of Science:
- Immunology
- Mathematical Biology
- Oncology
Background:
- Immune checkpoint inhibitors like anti-PD-1 enhance adaptive immunity against tumors.
- Oncolytic viruses (OV) stimulate innate immunity to eliminate infected tumor cells.
- Combining these therapies may improve tumor reduction through synergistic immune activation.
Purpose of the Study:
- To investigate the interaction between adaptive and innate immunities under OV and anti-PD-1 treatment.
- To identify key factors influencing tumor reduction based on varying immune strengths.
- To determine optimal treatment protocols for patients with different immune profiles.
Main Methods:
- Development of a mathematical model simulating tumor-immune interactions.
- Creation of virtual baseline and cohort patients with varying immunity strengths.
- Global sensitivity analysis to assess the impact of different parameters on treatment outcomes.
Main Results:
- Adaptive immunity exerts greater control over treatment outcomes than innate immunity.
- Treatment efficacy is sensitive to OV dosage and the balance of infected cell clearance by T cells.
- OV treatment is more sensitive to adaptive than innate immunity, and anti-PD-1 efficacy is amplified with stronger adaptive immunity.
Conclusions:
- Tumor reduction is significantly influenced by the interplay of adaptive and innate immunity.
- Anti-PD-1 can either enhance or counteract OV efficacy depending on OV dosage and host immune status.
- Tailoring treatment protocols based on individual immune strength is crucial for optimizing therapeutic outcomes.
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