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PLoS One. 2013 Sep 11;8(9):e73759. doi: 10.1371/journal.pone.0073759. eCollection 2013.

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

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1
Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.

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.

PMID:
24040057
PMCID:
PMC3770695
DOI:
10.1371/journal.pone.0073759
[Indexed for MEDLINE]
Free PMC Article
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