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Mechanistic Modeling of a Novel Oncolytic Virus, V937, to Describe Viral Kinetic and Dynamic Processes Following

Zinnia P Parra-Guillen1,2, Tomoko Freshwater3, Youfang Cao3

  • 1Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.

Frontiers in Pharmacology
|August 9, 2021
PubMed

Insights

V937, a novel oncolytic Coxsackievirus A21, effectively shrinks tumors in preclinical models. This mechanistic model quantifies viral kinetics and anti-tumor effects, aiding oncolytic virus development.

Area of Science:

  • Virology
  • Oncology
  • Pharmacokinetics

Background:

  • V937 is an investigational oncolytic Coxsackievirus A21 targeting solid tumors.
  • It infects tumor cells expressing the ICAM-1 receptor, leading to cell lysis.
  • Advanced solid tumors represent a significant unmet medical need.

Purpose of the Study:

  • To develop a mechanistic model for V937 viral kinetics and dynamics.
  • To quantitatively analyze viral distribution, replication, and anti-tumor response.
  • To support the clinical development of V937 as an oncolytic virus therapy.

Main Methods:

  • Integrated in vitro and in vivo data from six preclinical studies.
  • Utilized human xenograft models in immunodeficient mice.
  • Administered V937 intratumorally and intravenously.

Main Results:

  • Developed a model to quantitatively analyze V937 biological processes.
  • In vitro estimates accurately predicted in vivo tumor response.
  • Observed significant tumor shrinkage with both administration routes despite rapid systemic clearance.

Conclusions:

  • The mechanistic model provides quantitative insights into V937's behavior.
  • V937 demonstrates oncolytic potential in preclinical models, warranting further clinical investigation.
  • The framework can be expanded to include immune system interactions for enhanced oncolytic virus development.
Keywords:
mechanistic modelingoncolytic virustumor distributionviral dynamicsviral kinetics

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