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Titolo:
RECOMBINANT IL-12 ADMINISTRATION INDUCES TUMOR-REGRESSION IN ASSOCIATION WITH IFN-GAMMA PRODUCTION
Autore:
NASTALA CL; EDINGTON HD; MCKINNEY TG; TAHARA H; NALESNIK MA; BRUNDA MJ; GATELY MK; WOLF SF; SCHREIBER RD; STORKUS WJ; LOTZE MT;
Indirizzi:
UNIV PITTSBURGH,DEPT SURG,W 1540 BIOMED SCI TOWER,200 LOTHROP ST PITTSBURGH PA 15261 UNIV PITTSBURGH,DEPT SURG PITTSBURGH PA 15261 UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM PITTSBURGH PA 15261 UNIV PITTSBURGH,DEPT PATHOL PITTSBURGH PA 00000 HOFFMANN LA ROCHE INC NUTLEY NJ 07110 GENET INST INC CAMBRIDGE MA 02140 WASHINGTON UNIV ST LOUIS MO 00000
Titolo Testata:
The Journal of immunology
fascicolo: 4, volume: 153, anno: 1994,
pagine: 1697 - 1706
SICI:
0022-1767(1994)153:4<1697:RIAITI>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL STIMULATORY FACTOR; NATURAL-KILLER-CELL; LYMPHOCYTE MATURATION FACTOR; INTERFERON-GAMMA; T-CELLS; HETERODIMERIC CYTOKINE; FACTOR INTERLEUKIN-12; NECROSIS-FACTOR; MESSENGER-RNAS; FACTOR NKSF;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
C.L. Nastala et al., "RECOMBINANT IL-12 ADMINISTRATION INDUCES TUMOR-REGRESSION IN ASSOCIATION WITH IFN-GAMMA PRODUCTION", The Journal of immunology, 153(4), 1994, pp. 1697-1706

Abstract

Recent evidence supports the critical and proximate role of IL-12 in regulating both T and NK cell function during inflammation. In these studies, we evaluated the in vivo antitumor activity of murine IL-12 inmurine adenocarcinoma and sarcoma models using both systemic and peritumoral administration. Antitumor effects were consistently demonstrated both in models of microdisease, in which IL-12 treatment was initiated soon after tumor inoculation (1 to 5 days), and in animals bearinglarge established tumors (7 to 14 days). Treatment with IL-12 markedly prolonged survival and, in most cases, caused complete tumor regression. Significant reduction in pulmonary metastases after systemic treatment was observed when treatment was delayed for 10 days after tumor inoculation. Increases in serum IFN-gamma, TNF-alpha, and nitrogen oxides were demonstrated, exceeding those observed with IL-2 treatment. Systemic administration of anti-IFN-gamma Abs before IL-12 treatment nearly completely abrogated the antitumor effect in experiments using subcutaneous tumors or pulmonary metastases. Depletion of the individualT cell subsets CD4 and CD8 by systemic administration of mAbs diminished the effectiveness of IL-12 when administered in combination. An infiltrate composed primarily of CD8(+)+ cells was demonstrated by usingimmunohistochemical analysis of tumors after IL-12 treatment. Minimalapparent toxicity was demonstrated at effective doses (0.1 to 1.0 mu g/day) of IL-12. These results indicate that IL-12 is an effective andminimally toxic antitumor agent in murine tumor models and leads to an immune-mediated rejection involving, at least in part, IFN-gamma, CD4(+), and CD8(+) cells. Human clinical trials of IL-12 for the treatment of malignancy are supported by these studies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 13:50:19