1. Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues
- Author
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Anja Kipar, Simona Bramante, Anniina Koski, Akseli Hemminki, Anna Kanerva, Timo Joensuu, Lotta Vassilev, Minna Oksanen, Juuso Juhila, Department of Pathology, Medicum, Faculty of Medicine, University of Helsinki, Departments of Faculty of Veterinary Medicine, Akseli Eetu Hemminki / Principal Investigator, Department of Obstetrics and Gynecology, and Clinicum
- Subjects
Male ,Pathology ,Time Factors ,medicine.medical_treatment ,Gene Dosage ,Antibodies, Viral ,medicine.disease_cause ,Transduction, Genetic ,Neoplasms ,Drug Discovery ,Tissue Distribution ,Child ,REPLICATING ADENOVIRUS ,Cause of death ,Oncolytic Virotherapy ,I CLINICAL-TRIAL ,Middle Aged ,CHEMOTHERAPY ,3. Good health ,Oncolytic Viruses ,PHASE-I ,Child, Preschool ,Molecular Medicine ,Female ,Original Article ,Autopsy ,REFRACTORY SOLID TUMORS ,Adult ,Oncolytic adenovirus ,medicine.medical_specialty ,Adolescent ,Genetic Vectors ,3122 Cancers ,CANCER-PATIENTS ,Virus ,OVARIAN-CANCER ,Adenoviridae ,Viral Proteins ,Young Adult ,Cell Line, Tumor ,medicine ,Genetics ,Humans ,IMMUNOTHERAPY ,Molecular Biology ,Aged ,Pharmacology ,Chemotherapy ,business.industry ,Granulocyte-Macrophage Colony-Stimulating Factor ,GM-CSF ,Genetic Therapy ,Immunotherapy ,medicine.disease ,Antibodies, Neutralizing ,ONYX-015 ,Oncolytic virus ,DNA, Viral ,Immunology ,3111 Biomedicine ,business ,Ovarian cancer - 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.
- Published
- 2015
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