title: Mathematical model for radial expansion and conflation of intratumoral infectious centers predicts curative oncolytic virotherapy parameters.
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.
authors.affiliation: Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Kent
authors.initials: K
authors.lastname: Bailey
authors.forename: Amber
authors.initials: A
authors.lastname: Kirk
authors.forename: Shruthi
authors.initials: S
authors.lastname: Naik
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nace
authors.forename: Michael B
authors.initials: MB
authors.lastname: Steele
authors.forename: Lukkana
authors.initials: L
authors.lastname: Suksanpaisan
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Federspiel
authors.forename: Kah-Whye
authors.initials: KW
authors.lastname: Peng
authors.forename: David
authors.initials: D
authors.lastname: Kirk
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
mesh_terms: D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D008954:Models, Biological; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000276:immunology / Q000502:physiology; D047368:Tumor Burden / Q000276:immunology; D014709:Vero Cells; D018116:Vesiculovirus / Q000276:immunology / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
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