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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-1-29
pubmed:abstractText
We have documented previously that adenovirus-mediated interleukin 12 (IL-12) gene therapy is effective for orthotopic tumor control and suppression of pre-established metastases in a preclinical prostate cancer model (Y. Nasu et al., Gene Ther., 6: 338-349, 1999). In this report, we directly compare the effectiveness of an adenovirus that expresses both IL-12 and the costimulatory molecule B7-1 (AdmIL12/B7) with one that expresses IL-12 alone (AdmIL-12) using the poorly immunogenic RM-9 orthotopic murine model of prostate cancer. We document AdmIL-12/B7-mediated secretion of IL-12 and increased surface expression of B7-1 in infected RM-9 tumor cells. A significant reduction in orthotopic tumor size and increased survival was demonstrated in mice treated with a single orthotopic injection of AdmIL-12/B7 compared with AdmIL-12 or controls. Six of 19 animals treated with AdmIL-12/B7 survived long term with apparent eradication of the primary tumor in contrast to one of 38 animals in the AdmIL-12-treated group. Orthotopic treatment of tumors with both vectors led to an infiltration of both CD4+ and CD8+ immunoreactive cells, with AdmIL-12/B7 treatment having a more prolonged infiltration of CD8+ cells. AdmIL-12/B7 was also more effective than AdmIL-12 or controls at suppression of pre-established metastases. We further developed a vaccine model based on s.c. injection of infected, irradiated RM-9 cells and found that both AdmIL-12 and AdmIL-12/B7 are effective at suppressing the development and growth of challenge orthotopic tumors using this protocol.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4101-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11051263-Adenoviridae, pubmed-meshheading:11051263-Animals, pubmed-meshheading:11051263-Antigens, CD4, pubmed-meshheading:11051263-Antigens, CD8, pubmed-meshheading:11051263-Antigens, CD80, pubmed-meshheading:11051263-Cancer Vaccines, pubmed-meshheading:11051263-Flow Cytometry, pubmed-meshheading:11051263-Gene Therapy, pubmed-meshheading:11051263-Humans, pubmed-meshheading:11051263-Immunohistochemistry, pubmed-meshheading:11051263-Interleukin-12, pubmed-meshheading:11051263-Kinetics, pubmed-meshheading:11051263-Lung Neoplasms, pubmed-meshheading:11051263-Male, pubmed-meshheading:11051263-Mice, pubmed-meshheading:11051263-Mice, Inbred C57BL, pubmed-meshheading:11051263-Neoplasm Transplantation, pubmed-meshheading:11051263-Prostatic Neoplasms, pubmed-meshheading:11051263-Time Factors, pubmed-meshheading:11051263-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Prostate cancer gene therapy: comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines.
pubmed:affiliation
Scott Department of Urology Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.