Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy: A Mathematical model

Yangjin Kim, Hyun Geun Lee, Nina Dmitrieva, Junseok Kim, Balveen Kaur, Avner Friedman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.

Original languageEnglish
Article numbere102499
JournalPLoS One
Volume9
Issue number7
DOIs
Publication statusPublished - 2014 Jul 21

Fingerprint

Oncolytic Viruses
Viruses
Tumors
Theoretical Models
mathematical models
Mathematical models
Chondroitin ABC Lyase
viruses
neoplasms
Neoplasms
Cells
Glioma
Military electronic countermeasures
injection
Satellites
chondroitin sulfate
Injections
proteoglycans
Chondroitin Sulfates
Proteoglycans

ASJC Scopus subject areas

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

Cite this

Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy : A Mathematical model. / Kim, Yangjin; Lee, Hyun Geun; Dmitrieva, Nina; Kim, Junseok; Kaur, Balveen; Friedman, Avner.

In: PLoS One, Vol. 9, No. 7, e102499, 21.07.2014.

Research output: Contribution to journalArticle

Kim, Yangjin ; Lee, Hyun Geun ; Dmitrieva, Nina ; Kim, Junseok ; Kaur, Balveen ; Friedman, Avner. / Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy : A Mathematical model. In: PLoS One. 2014 ; Vol. 9, No. 7.
@article{a9d726933f6745c5b84b2365179cddaa,
title = "Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy: A Mathematical model",
abstract = "Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.",
author = "Yangjin Kim and Lee, {Hyun Geun} and Nina Dmitrieva and Junseok Kim and Balveen Kaur and Avner Friedman",
year = "2014",
month = "7",
day = "21",
doi = "10.1371/journal.pone.0102499",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy

T2 - A Mathematical model

AU - Kim, Yangjin

AU - Lee, Hyun Geun

AU - Dmitrieva, Nina

AU - Kim, Junseok

AU - Kaur, Balveen

AU - Friedman, Avner

PY - 2014/7/21

Y1 - 2014/7/21

N2 - Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.

AB - Oncolytic viruses are genetically engineered viruses that are designed to kill cancer cells while doing minimal damage to normal healthy tissue. After being injected into a tumor, they infect cancer cells, multiply inside them, and when a cancer cell is killed they move on to spread and infect other cancer cells. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove a major glioma ECM component, chondroitin sulfate glycosoamino glycans from proteoglycans without any deleterious effects in vivo. It has been shown that Chase-ABC treatment is able to promote the spread of the viruses, increasing the efficacy of the viral treatment. In this paper we develop a mathematical model to investigate the effect of the Chase-ABC on the treatment of glioma by oncolytic viruses (OV). We show that the model's predictions agree with experimental results for a spherical glioma. We then use the model to test various treatment options in the heterogeneous microenvironment of the brain. The model predicts that separate injections of OV, one into the center of the tumor and another outside the tumor will result in better outcome than if the total injection is outside the tumor. In particular, the injection of the ECM-degrading enzyme (Chase-ABC) on the periphery of the main tumor core need to be administered in an optimal strategy in order to infect and eradicate the infiltrating glioma cells outside the tumor core in addition to proliferative cells in the bulk of tumor core. The model also predicts that the size of tumor satellites and distance between the primary tumor and multifocal/satellite lesions may be an important factor for the efficacy of the viral therapy with Chase treatment.

UR - http://www.scopus.com/inward/record.url?scp=84904567760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904567760&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0102499

DO - 10.1371/journal.pone.0102499

M3 - Article

C2 - 25047810

AN - SCOPUS:84904567760

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e102499

ER -