Mathematical model for radial expansion and conflation of intratumoral infectious centers predicts curative oncolytic virotherapy parameters

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

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Article numbere73759
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 11 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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