Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues

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dc.contributor.author Koski, Anniina
dc.contributor.author Bramante, Simona
dc.contributor.author Kipar, Anja
dc.contributor.author Oksanen, Minna
dc.contributor.author Juhila, Juuso
dc.contributor.author Vassilev, Lotta
dc.contributor.author Joensuu, Timo
dc.contributor.author Kanerva, Anna
dc.contributor.author Hemminki, Akseli
dc.date.accessioned 2019-09-12T05:00:01Z
dc.date.available 2019-09-12T05:00:01Z
dc.date.issued 2015-10
dc.identifier.citation Koski , A , Bramante , S , Kipar , A , Oksanen , M , Juhila , J , Vassilev , L , Joensuu , T , Kanerva , A & Hemminki , A 2015 , ' Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues ' , Molecular therapy , vol. 23 , no. 10 , pp. 1641-1652 . https://doi.org/10.1038/mt.2015.125
dc.identifier.other PURE: 54812106
dc.identifier.other PURE UUID: dc6747d7-ac82-4a98-8be6-47f2ad879921
dc.identifier.other WOS: 000362508100012
dc.identifier.other Scopus: 84943588225
dc.identifier.other ORCID: /0000-0003-3601-2786/work/61594083
dc.identifier.uri http://hdl.handle.net/10138/305394
dc.description.abstract In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof Molecular therapy
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject REFRACTORY SOLID TUMORS
dc.subject I CLINICAL-TRIAL
dc.subject CANCER-PATIENTS
dc.subject PHASE-I
dc.subject GM-CSF
dc.subject REPLICATING ADENOVIRUS
dc.subject OVARIAN-CANCER
dc.subject IMMUNOTHERAPY
dc.subject CHEMOTHERAPY
dc.subject ONYX-015
dc.subject 3122 Cancers
dc.subject 3111 Biomedicine
dc.title Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues en
dc.type Article
dc.contributor.organization Department of Pathology
dc.contributor.organization Medicum
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.contributor.organization Departments of Faculty of Veterinary Medicine
dc.contributor.organization Akseli Eetu Hemminki / Principal Investigator
dc.contributor.organization Department of Obstetrics and Gynecology
dc.contributor.organization Clinicum
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/mt.2015.125
dc.relation.issn 1525-0016
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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