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Mathematical Modeling of Oncolytic Virus Therapy Reveals Role of the Immune Response

Ela Guo1, Hana M Dobrovolny1

  • 1Department of Physics & Astronomy, Texas Christian University, Fort Worth, TX 76109, USA.

Viruses
|September 28, 2023
PubMed

Insights

Oncolytic adenoviruses (OAds) show promise in cancer therapy by targeting tumor cells and boosting immunity. Mathematical modeling reveals that an immune response is crucial for tumor elimination and identifies key viral characteristics for effective OAd cancer treatment.

Area of Science:

  • Oncology
  • Virology
  • Mathematical Biology

Background:

  • Oncolytic adenoviruses (OAds) are engineered viruses that selectively infect and destroy cancer cells.
  • OAds also possess the ability to stimulate an anti-tumor immune response, enhancing their therapeutic potential.
  • Previous research has explored the efficacy of OAds in various cancer models.

Purpose of the Study:

  • To parameterize an ordinary differential equation (ODE) model of tumor growth inhibition by OAds.
  • To investigate the effects of genetically re-engineered OAds on A549 lung cancer tumors in murine models.
  • To identify key viral characteristics associated with OAd efficacy.

Main Methods:

  • Utilized an ordinary differential equation (ODE) model to simulate tumor growth dynamics.
  • Applied the model to data from experiments involving OAds and A549 lung cancer in mice.
  • Analyzed parameter estimates to determine factors influencing OAd effectiveness.

Main Results:

  • The model best fit the data when incorporating an immune response component.
  • The immune response was identified as a significant mechanism for tumor elimination.
  • Effective OAds were characterized by high infection rates and low viral clearance rates, correlating with delayed tumor growth.

Conclusions:

  • Mathematical modeling supports the role of immune response in OAd cancer therapy.
  • Specific viral characteristics, such as high infectivity and slow clearance, are linked to improved tumor growth delay.
  • Further research on modified OAds (e.g., E1A and P19 recombined viruses) in diverse tumor microenvironments is warranted.
Keywords:
cancerimmune responseinterferonmathematical modelparameter estimation

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