Open AccessMathematical Model for Radial Expansion and Conflation of Intratumoral Infectious Centers Predicts Curative Oncolytic Virotherapy Parameters
Author(s) -
Kent R. Bailey,
Amber C. Kirk,
Shruthi Naik,
Rebecca Nace,
Michael B. Steele,
Lukkana Suksanpaisan,
Xing Li,
Mark J. Federspiel,
Kah Whye Peng,
D. Kirk,
Stephen J. Russell
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0073759
Subject(s) - oncolytic virus , virotherapy , vesicular stomatitis virus , multiple myeloma , virus , virology , biology , cancer research , immunology
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.