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dc.contributor.authorAnnels, NEen_US
dc.contributor.authorMansfield, Den_US
dc.contributor.authorArif, Men_US
dc.contributor.authorBallesteros-Merino, Cen_US
dc.contributor.authorSimpson, GRen_US
dc.contributor.authorDenyer, Men_US
dc.contributor.authorSandhu, SSen_US
dc.contributor.authorMelcher, AAen_US
dc.contributor.authorHarrington, KJen_US
dc.contributor.authorDavies, Ben_US
dc.contributor.authorAu, Gen_US
dc.contributor.authorGrose, Men_US
dc.contributor.authorBagwan, Ien_US
dc.contributor.authorFox, Ben_US
dc.contributor.authorVile, Ren_US
dc.contributor.authorMostafid, Hen_US
dc.contributor.authorShafren, Den_US
dc.contributor.authorPandha, HSen_US
dc.date.accessioned2019-07-22T14:25:01Z
dc.date.issued2019-10
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (19), pp. 5818 - 5831
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3302
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-18-4022
dc.description.abstractPURPOSE:The CANON [CAVATAK in NON-muscle-invasive bladder cancer (NMIBC)] study evaluated a novel ICAM-1-targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer. PATIENTS AND METHODS:Fifteen patients enrolled in this "window of opportunity" phase I study, exposing primary bladder cancers to CAVATAK prior to surgery. The first 9 patients received intravesical administration of monotherapy CAVATAK; in the second stage, 6 patients received CAVATAK with a subtherapeutic dose of mitomycin C, known to enhance expression of ICAM-1 on bladder cancer cells. The primary endpoint was to determine patient safety and maximum tolerated dose (MTD). Secondary endpoints were evidence of viral replication, induction of inflammatory cytokines, antitumor activity, and viral-induced changes in resected tissue. RESULTS:Clinical activity of CAVATAK was demonstrated by induction of tumor inflammation and hemorrhage following either single or multiple administrations of CAVATAK in multiple patients, and a complete resolution of tumor in 1 patient. Whether used alone or in combination with mitomycin C, CAVATAK caused marked inflammatory changes within NMIBC tissue biopsies by upregulating IFN-inducible genes, including both immune checkpoint inhibitory genes (PD-L1 and LAG3) and Th1-associated chemokines, as well as the induction of the innate activator RIG-I, compared with bladder cancer tissue from untreated patients. No significant toxicities were reported in any patient, from either virus or combination therapy. CONCLUSIONS:The acceptable safety profile of CAVATAK, proof of viral targeting, replication, and tumor cell death together with the virus-mediated increases in "immunological heat" within the tumor microenvironment all indicate that CAVATAK may be potentially considered as a novel therapeutic for NMIBC.
dc.formatPrint-Electronic
dc.format.extent5818 - 5831
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectHumans
dc.subjectIntercellular Adhesion Molecule-1
dc.subjectImmunotherapy
dc.subjectAdministration, Intravesical
dc.subjectFeasibility Studies
dc.subjectMaximum Tolerated Dose
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectOncolytic Virotherapy
dc.subjectOncolytic Viruses
dc.subjectUrinary Bladder Neoplasms
dc.subjectMolecular Targeted Therapy
dc.subjectTumor Microenvironment
dc.titlePhase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder Cancer.
dc.typeJournal Article
dcterms.dateAccepted2019-06-27
rioxxterms.versionofrecord10.1158/1078-0432.ccr-18-4022
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue19
pubs.notes12 months
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL)
pubs.publication-statusPublished
pubs.volume25en_US
pubs.embargo.terms12 months
icr.researchteamTargeted Therapyen_US
icr.researchteamTranslational Immunotherapyen_US
dc.contributor.icrauthorMansfield, Daviden
dc.contributor.icrauthorHarrington, Kevinen
dc.contributor.icrauthorMelcher, Alanen


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