Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
1995-6-29
|
| pubmed:abstractText |
Our recent studies using IL-12 protein or fibroblasts genetically engineered to secrete IL-12 have demonstrated profound antitumor effects of IL-12 in murine models. The antitumor effects of local, high level IL-12 expression were examined using a retroviral vector, which can express both IL-12 subunits (p35 and p40) and the neomycin phosphotransferase (Neo)-marker gene from a polycistronic message utilizing internal ribosome entry site sequences. All animals intradermally (i.d.) receiving MCA207 murine sarcoma cell line nontransfected or Neo-transfected had progressively growing tumor, whereas all animals injected with MCA207 transfected with IL-12 were tumor free and were subsequently determined to be immune to a rechallenge of nontransfected MCA207 i.d. Similar results were obtained in experiments using the poorly immunogenic MCA102 murine sarcoma cell line. The inoculation of live MCA207-IL-12 tumor cells also caused the regression of contralateral nontransfected MCA207 inoculated either at the same time (80% protection) or up to 3 days before (33% protection) to the therapeutic tumor inoculation. In vivo depletion studies suggest that NK cells and IFN-gamma play important roles in the development of the early phase of the antitumor response, but that T cells (both CD4+ and CD8+) play the major role in the subsequent events, leading to long-term immunity. The potent antitumor effects observed for paracrine gene-delivered administration of IL-12 have thus been confirmed for multiple tumor cell types and in multiple murine strains. We believe that these results support the feasibility of IL-12 gene therapy for the treatment of human cancer.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
154
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
6466-74
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7759882-Animals,
pubmed-meshheading:7759882-CD4-Positive T-Lymphocytes,
pubmed-meshheading:7759882-CD8-Positive T-Lymphocytes,
pubmed-meshheading:7759882-Female,
pubmed-meshheading:7759882-Gene Expression,
pubmed-meshheading:7759882-Gene Therapy,
pubmed-meshheading:7759882-Genetic Vectors,
pubmed-meshheading:7759882-Interleukin-12,
pubmed-meshheading:7759882-Killer Cells, Natural,
pubmed-meshheading:7759882-Lymphocyte Depletion,
pubmed-meshheading:7759882-Mice,
pubmed-meshheading:7759882-Mice, Inbred C57BL,
pubmed-meshheading:7759882-Neoplasms, Experimental,
pubmed-meshheading:7759882-Neutralization Tests,
pubmed-meshheading:7759882-Retroviridae,
pubmed-meshheading:7759882-Sarcoma, Experimental,
pubmed-meshheading:7759882-Transfection,
pubmed-meshheading:7759882-Tumor Necrosis Factor-alpha
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Effective eradication of established murine tumors with IL-12 gene therapy using a polycistronic retroviral vector.
|
| pubmed:affiliation |
Department of Surgery, School of Medicine, Pittsburgh Cancer Institute, University of Pittsburgh, PA 15213, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|