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Article: Validation and analysis of a mathematical model of a replication-competent oncolytic virus for cancer treatment: Implications for virus design and delivery

TitleValidation and analysis of a mathematical model of a replication-competent oncolytic virus for cancer treatment: Implications for virus design and delivery
Authors
Issue Date2003
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2003, v. 63 n. 6, p. 1317-1324 How to Cite?
AbstractMotivated by the rapid expansion in the development of replication-competent viral agents for the treatment of solid tumors, we formulated and analyzed a three-dimensional mathematical model of a tumor that is infected by a replication-competent virus. We initially considered three patterns of intratumoral injection in which a fixed fraction of cells are initially infected with the virus throughout (a) the entire tumor, (b) the tumor core, and (c) the tumor rim, respectively. For each injection pattern, an approximate analysis of the model provides a simple and accurate condition for whether the virus will eradicate the tumor. The model was then generalized to incorporate nutrient-limited necrosis and an innate immune response against virus-infected tumor cells. Recent preclinical and clinical data were used to validate the model and estimate key parameter values. Our analysis has the following implications: even in the absence of an immune response, tumor eradication requires widespread distribution of the virus within the tumor at the time of infection; core or rim injections alone may result in tumor escape, particularly in a well-vascularized tumor; the more rapidly a virus lyses infected cells the more effective it will be at controlling the tumor; and the innate immune response to the virus can potentially prevent the virus from controlling the tumor, even with repeat injections. Therefore, in addition to diffuse intratumoral infection, tumor eradication by oncolytic adenovirus will probably require potent suppression of innate immune clearance mechanisms (e.g., by replacement of adenovirus E3 genes), combinations with traditional (chemotherapy, radiotherapy) treatments, and/or concomitant therapeutic gene expression with resultant bystander effects.
Persistent Identifierhttp://hdl.handle.net/10722/151575
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWein, LMen_US
dc.contributor.authorWu, JTen_US
dc.contributor.authorKirn, DHen_US
dc.date.accessioned2012-06-26T06:24:52Z-
dc.date.available2012-06-26T06:24:52Z-
dc.date.issued2003en_US
dc.identifier.citationCancer Research, 2003, v. 63 n. 6, p. 1317-1324en_US
dc.identifier.issn0008-5472en_US
dc.identifier.urihttp://hdl.handle.net/10722/151575-
dc.description.abstractMotivated by the rapid expansion in the development of replication-competent viral agents for the treatment of solid tumors, we formulated and analyzed a three-dimensional mathematical model of a tumor that is infected by a replication-competent virus. We initially considered three patterns of intratumoral injection in which a fixed fraction of cells are initially infected with the virus throughout (a) the entire tumor, (b) the tumor core, and (c) the tumor rim, respectively. For each injection pattern, an approximate analysis of the model provides a simple and accurate condition for whether the virus will eradicate the tumor. The model was then generalized to incorporate nutrient-limited necrosis and an innate immune response against virus-infected tumor cells. Recent preclinical and clinical data were used to validate the model and estimate key parameter values. Our analysis has the following implications: even in the absence of an immune response, tumor eradication requires widespread distribution of the virus within the tumor at the time of infection; core or rim injections alone may result in tumor escape, particularly in a well-vascularized tumor; the more rapidly a virus lyses infected cells the more effective it will be at controlling the tumor; and the innate immune response to the virus can potentially prevent the virus from controlling the tumor, even with repeat injections. Therefore, in addition to diffuse intratumoral infection, tumor eradication by oncolytic adenovirus will probably require potent suppression of innate immune clearance mechanisms (e.g., by replacement of adenovirus E3 genes), combinations with traditional (chemotherapy, radiotherapy) treatments, and/or concomitant therapeutic gene expression with resultant bystander effects.en_US
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_US
dc.relation.ispartofCancer Researchen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshNeoplasms - Therapy - Virologyen_US
dc.subject.meshReproducibility Of Resultsen_US
dc.subject.meshSpheroids, Cellularen_US
dc.subject.meshVirus Physiological Phenomenaen_US
dc.subject.meshVirus Replicationen_US
dc.titleValidation and analysis of a mathematical model of a replication-competent oncolytic virus for cancer treatment: Implications for virus design and deliveryen_US
dc.typeArticleen_US
dc.identifier.emailWu, JT:joewu@hkucc.hku.hken_US
dc.identifier.authorityWu, JT=rp00517en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid12649193-
dc.identifier.scopuseid_2-s2.0-0037444281en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037444281&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume63en_US
dc.identifier.issue6en_US
dc.identifier.spage1317en_US
dc.identifier.epage1324en_US
dc.identifier.isiWOS:000181702300027-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWein, LM=35560766400en_US
dc.identifier.scopusauthoridWu, JT=7409256423en_US
dc.identifier.scopusauthoridKirn, DH=7006444499en_US

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