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Mathematical Model for Radial Expansion and Conflation of Intratumoral Infectious Centers Predicts Curative Oncolytic Virotherapy Parameters

Author

Listed:
  • Kent Bailey
  • Amber Kirk
  • Shruthi Naik
  • Rebecca Nace
  • Michael B Steele
  • Lukkana Suksanpaisan
  • Xing Li
  • Mark J Federspiel
  • Kah-Whye Peng
  • David Kirk
  • Stephen J Russell

Abstract

Simple, inductive mathematical models of oncolytic virotherapy are needed to guide protocol design and improve treatment outcomes. Analysis of plasmacytomas regressing after a single intravenous dose of oncolytic vesicular stomatitis virus in myeloma animal models revealed that intratumoral virus spread was spatially constrained, occurring almost exclusively through radial expansion of randomly distributed infectious centers. From these experimental observations we developed a simple model to calculate the probability of survival for any cell within a treated tumor. The model predicted that small changes to the density of initially infected cells or to the average maximum radius of infected centers would have a major impact on treatment outcome, and this was confirmed experimentally. The new model provides a useful and flexible tool for virotherapy protocol optimization.

Suggested Citation

  • Kent Bailey & Amber Kirk & Shruthi Naik & Rebecca Nace & Michael B Steele & Lukkana Suksanpaisan & Xing Li & Mark J Federspiel & Kah-Whye Peng & David Kirk & Stephen J Russell, 2013. "Mathematical Model for Radial Expansion and Conflation of Intratumoral Infectious Centers Predicts Curative Oncolytic Virotherapy Parameters," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-11, September.
    • Handle: RePEc:plo:pone00:0073759
    DOI: 10.1371/journal.pone.0073759
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    Cited by:

    1. Ignacio A Rodriguez-Brenes & Andrew Hofacre & Hung Fan & Dominik Wodarz, 2017. "Complex Dynamics of Virus Spread from Low Infection Multiplicities: Implications for the Spread of Oncolytic Viruses," PLOS Computational Biology, Public Library of Science, vol. 13(1), pages 1-19, January.

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