Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-11-20
pubmed:abstractText
Human adenoviruses have been developed as an attractive vehicle for in vivo liver-directed gene therapy. Problems with the application of first generation recombinant adenoviruses to liver-directed gene therapy have been transient expression of the recombinant gene and development of hepatitis. Previous studies in mouse models of gene transfer to liver and lung suggested that MHC class I-restricted cytotoxic T lymphocytes (CTLs) to viral antigens may be effectors in the elimination of transgene expression. The goal of this study was to evaluate the importance of viral antigens versus transgene product in inducing CTL mediated hepatocyte destruction in vivo. Immunization of C57BL/6 mice with a lacZ-expressing adenovirus elicited CTL responses to both viral antigens and the transgene product, beta-galactosidase (beta-gal). Adoptive transfer experiments, as well as studies involving lacZ-transgenic mice (ROSA-26) revealed that CTLs to viral antigens are sufficient to destroy virus-infected hepatocytes, indicating that CTLs to beta-gal can not solely account for the observed hepatocyte destruction that has characterized the use of first generation viruses. In addition, we confirmed that B cell-mediated events do not participate in destruction of hepatocytes in vivo, despite the production of virus- and beta-gal-specific antibodies. These data confirm the hypothesis that viral gene expression elicits host responses that contribute to the problem of transgene instability. Recombinant adenoviruses must be redesigned to diminish viral gene expression if they are to be used in the treatment of chronic diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
137-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo.
pubmed:affiliation
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania, Philadelphia, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't