title: Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues.
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.
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Anniina
authors.initials: A
authors.lastname: Koski
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Simona
authors.initials: S
authors.lastname: Bramante
authors.affiliation: Finnish Centre for Laboratory Animal Pathology, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.|School of Veterinary Science and Department of Infection Biology, Institute of Global Health, University of Liverpool, Liverpool, UK.|Present address: Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Kipar
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Oksanen
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Juuso
authors.initials: J
authors.lastname: Juhila
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Vassilev
authors.affiliation: Docrates Hospital, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Joensuu
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.|Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.affiliation: Cancer Gene Therapy Group, Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.|Docrates Hospital, Helsinki, Finland.|TILT Biotherapeutics Ltd., Helsinki, Finland.|Department of Oncology, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001344:Autopsy; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral; D005260:Female; D018628:Gene Dosage; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D014764:Viral Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor