Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-2-21
pubmed:abstractText
Recent studies have shown that gene therapy with type I interferon (IFN) in an adenovirus vector is a powerful tool to suppress the growth of human tumors transplanted in immune-deficient mice. However, in these studies the host immune-mediated effects, which may be important in mediating the long-term control of tumor growth by these cytokines, was not studied. In this paper, we evaluate the antitumor efficacy of different adenoviral vectors containing mouse IFN-alpha genes (i.e., a first-generation replication-defective vector containing IFN-alpha1 and two different second-generation vectors containing IFN-alpha2) in immunocompetent DBA/2 mice transplanted with highly metastatic Friend leukemic cells resistant in vitro to type I IFN. We found that injection of all the different adenovirus vectors containing mouse IFN-alpha( genes resulted in a marked antitumor response in mice transplanted either subcutaneously or intravenously with IFN-resistant Friend leukemic cells compared to tumor-bearing animals inoculated with a control vector. Tumor growth inhibition after injection of IFN-adenovirus vectors was associated with a prolonged presence of high IFN levels in the sera of the injected mice. Suppression of metastatic tumor growth was also observed after a single injection of the IFN--adenovirus recombinant vectors, whereas a comparable antitumor response generally required several injections of high doses of IFN. Altogether, these results demonstrate that IFN--adenoviral vectors can efficiently inhibit metastatic tumor growth by host-mediated mechanisms and suggest that adenovirus-mediated IFN-alpha gene therapy may represent an attractive alternative to the conventional clinical use of this cytokine, which generally requires multiple injections of high IFN doses for a prolonged period of time.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
63-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11219495-Adenoviridae, pubmed-meshheading:11219495-Animals, pubmed-meshheading:11219495-Friend murine leukemia virus, pubmed-meshheading:11219495-Gene Therapy, pubmed-meshheading:11219495-Genetic Vectors, pubmed-meshheading:11219495-Injections, Intraperitoneal, pubmed-meshheading:11219495-Injections, Intravenous, pubmed-meshheading:11219495-Interferon-alpha, pubmed-meshheading:11219495-Lac Operon, pubmed-meshheading:11219495-Leukemia, Experimental, pubmed-meshheading:11219495-Liver Neoplasms, Experimental, pubmed-meshheading:11219495-Male, pubmed-meshheading:11219495-Mice, pubmed-meshheading:11219495-Mice, Inbred DBA, pubmed-meshheading:11219495-Mice, Nude, pubmed-meshheading:11219495-Neoplasm Metastasis, pubmed-meshheading:11219495-Neoplasm Transplantation, pubmed-meshheading:11219495-Survival Analysis, pubmed-meshheading:11219495-Transfection, pubmed-meshheading:11219495-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Antitumor activity of recombinant adenoviral vectors expressing murine IFN-alpha in mice injected with metastatic IFN-resistant tumor cells.
pubmed:affiliation
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't