Vector sequences are not detected in tumor tissue from research subjects with ornithine transcarbamylase deficiency who previously received adenovirus gene transfer
Gene Therapy Center; Division of Hematology/Oncology, Department of Pediatrics; Department of Microbiology and Physiology Systems
Aged; Carcinoma, Hepatocellular; Colorectal Neoplasms; Dependovirus; Female; Gene Transfer Techniques; Genetic Therapy; Humans; Liver Neoplasms; Middle Aged; Ornithine Carbamoyltransferase; Ornithine Carbamoyltransferase Deficiency Disease; Research Subjects
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Genetic Processes | Genetics | Molecular Genetics | Neoplasms | Nervous System Diseases | Therapeutics
A 66-year-old woman heterozygous for a mutation in the ornithine transcarbamylase gene (Otc) participated in a phase I gene therapy trial for OTC deficiency. She received an adenovirus (Ad) vector expressing the functional OTC gene by intraportal perfusion. Fourteen years later she developed and subsequently died of hepatocellular carcinoma. A second subject, a 45-year-old woman, enrolled in the same trial presented with colon cancer 15 years later. We sought to investigate a possible association between the development of a tumor and prior adenoviral gene transfer in these two subjects. We developed and validated a sensitive nested polymerase chain reaction assay for recovering recombinant Ad sequences from host tissues. Using this method, we could not detect any Ad vector DNA in either tumor or normal tissue from the two patients. Our results are informative in ruling out the possibility that the adenoviral vector might have contributed to the development of cancer in those two subjects.
DOI of Published Version
Hum Gene Ther. 2013 Sep;24(9):814-9. doi: 10.1089/hum.2013.118. Link to article on publisher's website
Human gene therapy
Zhong, Li; Li, Shaoyong; Li, Mengxin; Xie, Jun; Zhang, Yu; Lee, Brendan; Batshaw, Mark L.; Wilson, James M.; and Gao, Guangping, "Vector sequences are not detected in tumor tissue from research subjects with ornithine transcarbamylase deficiency who previously received adenovirus gene transfer" (2013). University of Massachusetts Medical School Faculty Publications. 543.