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Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues
- Source :
- Molecular Therapy. 23(10):1641-1652
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- 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
Subjects
Details
- ISSN :
- 15250016
- Volume :
- 23
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy
- Accession number :
- edsair.doi.dedup.....dc84b094b17e22dde4ad38476f003d73
- Full Text :
- https://doi.org/10.1038/mt.2015.125