Linked Life Data

15812228

Source:http://linkedlifedata.com/resource/pubmed/id/15812228

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-4-6
pubmed:abstractText
Interleukin-12 (IL-12) gene was shown to produce both IL-12 and p40 subunit. The excess production of the p40 subunit as a natural antagonist of IL-12 is a major obstacle of IL-12 gene-based cancer therapy. We previously reported that IL-12N220L gene, which selectively reduces the secretion of the p40 subunit, induces long-lasting stronger type 1 helper T cells (T(H)1) and cytotoxic T lymphocyte (CTL) immunity in hepatitis C virus (HCV) E2 DNA vaccination model and higher protection from challenge with tumor cells expressing E2 than IL-12 in a prophylactic setting. Here, we demonstrated that intratumoral injection of IL-12N220L-expressing adenovirus showed better tumor growth inhibition and higher survival rate than that of IL-12 or granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing adenovirus in a therapeutic setting. In particular, the mice cured by IL-12N220L treatment were protected against intravenous rechallenge of the same tumor cells better than those by IL-12 treatment. In addition, the enhanced antitumor activity of IL-12N220L was confirmed in B16F10 lung metastasis model, which correlated with the frequency of tumor-specific interferon (IFN)-gamma-secreting cells. When tested in CT26/NP tumor that expresses influenza nucleoprotein (NP) as a tumor antigen, IL-12N220L induced stronger NP-specific T(H)1 and CTL responses than IL-12, particularly at a later time point, indicating the generating long-term tumor-specific memory T-cell responses. Moreover, the potent antitumor effects of IL-12N220L were further augmented by combination with chemotherapy using farnesyltransferase inhibitor (FTI), LB42908. Taken together, our results suggest that IL-12N220L is superior to IL-12 in cancer immunotherapy, which can be further enhanced by combination with chemotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
328-38
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15812228-Adenoviridae, pubmed-meshheading:15812228-Alkyl and Aryl Transferases, pubmed-meshheading:15812228-Animals, pubmed-meshheading:15812228-Cell Line, Tumor, pubmed-meshheading:15812228-Drug Therapy, Combination, pubmed-meshheading:15812228-Farnesyltranstransferase, pubmed-meshheading:15812228-Gene Therapy, pubmed-meshheading:15812228-Genetic Vectors, pubmed-meshheading:15812228-Imidazoles, pubmed-meshheading:15812228-Immunoenzyme Techniques, pubmed-meshheading:15812228-Immunotherapy, pubmed-meshheading:15812228-Interferon-gamma, pubmed-meshheading:15812228-Interleukin-12, pubmed-meshheading:15812228-Interleukin-12 Subunit p40, pubmed-meshheading:15812228-Mice, pubmed-meshheading:15812228-Neoplasms, pubmed-meshheading:15812228-Nucleoproteins, pubmed-meshheading:15812228-Piperazines, pubmed-meshheading:15812228-Protein Subunits
pubmed:year
2005
pubmed:articleTitle
Enhancement of interleukin-12 gene-based tumor immunotherapy by the reduced secretion of p40 subunit and the combination with farnesyltransferase inhibitor.
pubmed:affiliation
National Research Laboratory, Department of Life Science, Pohang University of Science & Technology, Pohang 790-784, Korea.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't