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

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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

Title: Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues
Author: Koski, Anniina; Bramante, Simona; Kipar, Anja; Oksanen, Minna; Juhila, Juuso; Vassilev, Lotta; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli
Contributor: University of Helsinki, Department of Pathology
University of Helsinki, Department of Pathology
University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Medicum
University of Helsinki, Department of Pathology
University of Helsinki, Docrates Hospital
University of Helsinki, Akseli Eetu Hemminki / Principal Investigator
University of Helsinki, Medicum
Date: 2015-10
Language: eng
Number of pages: 12
Belongs to series: Molecular therapy
ISSN: 1525-0016
URI: http://hdl.handle.net/10138/305394
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.
Subject: REFRACTORY SOLID TUMORS
I CLINICAL-TRIAL
CANCER-PATIENTS
PHASE-I
GM-CSF
REPLICATING ADENOVIRUS
OVARIAN-CANCER
IMMUNOTHERAPY
CHEMOTHERAPY
ONYX-015
3122 Cancers
3111 Biomedicine
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