Linked Life Data

9200473

Source:http://linkedlifedata.com/resource/pubmed/id/9200473

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-7-14
pubmed:abstractText
IL-12 is a heterodimeric immunoregulatory cytokine composed of covalently linked p40 and p35 subunits and exhibits antitumor activity in a variety of laboratory models. The efficacy of systemically administered cytokines for cancer therapy is often limited by toxicity. The gene therapy approach provides a mechanism to achieve temporary and high local concentrations of cytokines within a tumor with less risk of systemic toxicity. We constructed replication-defective adenoviruses containing the murine IL-12 p40 subunit (Ad.mp40) or a bicistronic vector containing cDNAs for the p40 and p35 subunits (Ad.mIL-12). Murine MB49 bladder cancer cells infected with Ad.mIL-12 secrete high concentrations of biologically active IL-12, while those infected with Ad.mp40 produce the p40 homodimer. Tumors injected with Ad.mIL-12 show rapid increases in IL-12 and IFN-gamma expression over 2 to 5 days and a return to baseline by 7 to 14 days. Injection of tumors with Ad.mIL-12 (1 x 10(9) plaque-forming units) results in a complete tumor regression in all mice, while those treated with control adenovirus succumb to their tumor. Efficacy is reduced when studies are performed in mice depleted of CD4+ and CD8+ cells or in nude mice. Mice cured of their tumor by Ad.mIL-12 demonstrate specific protective immunity upon rechallenge. Ad.mp40 does not exhibit antitumor activity and may antagonize the activity of rIL-12 or Ad.mIL-12. In summary, gene therapy strategies for cancer using adenoviral vectors containing IL-12 are highly effective with no significant toxicity in mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
159
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
351-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Eradication of murine bladder carcinoma by intratumor injection of a bicistronic adenoviral vector carrying cDNAs for the IL-12 heterodimer and its inhibition by the IL-12 p40 subunit homodimer.
pubmed:affiliation
Dana-Farber Cancer Institute, Department of Urology, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.