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Titolo:
INTERLEUKIN-12 AND B7-1 COSTIMULATORY MOLECULE EXPRESSED BY AN ADENOVIRUS VECTOR ACT SYNERGISTICALLY TO FACILITATE TUMOR-REGRESSION
Autore:
PUTZER BM; HITT M; MULLER WJ; EMTAGE P; GAULDIE J; GRAHAM FL;
Indirizzi:
MCMASTER UNIV,DEPT BIOL,1280 MAIN ST W HAMILTON ON L8S 4K1 CANADA MCMASTER UNIV,DEPT BIOL HAMILTON ON L8S 4K1 CANADA MCMASTER UNIV,DEPT PATHOL HAMILTON ON L8S 4K1 CANADA
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 20, volume: 94, anno: 1997,
pagine: 10889 - 10894
SICI:
0027-8424(1997)94:20<10889:IABCME>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
EFFECTIVE ANTITUMOR IMMUNITY; T-LYMPHOCYTES; MURINE TUMORS; IN-VITRO; HETERODIMERIC CYTOKINE; ESTABLISHED TUMORS; INDUCTION; CELLS; IL-12; PROLIFERATION;
Keywords:
GENE THERAPY; IMMUNOTHERAPY; CYTOKINES; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
B.M. Putzer et al., "INTERLEUKIN-12 AND B7-1 COSTIMULATORY MOLECULE EXPRESSED BY AN ADENOVIRUS VECTOR ACT SYNERGISTICALLY TO FACILITATE TUMOR-REGRESSION", Proceedings of the National Academy of Sciences of the United Statesof America, 94(20), 1997, pp. 10889-10894

Abstract

Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host-tumor relationship involves immunomodulating cytokines and also the presence of costimulatory molecules, To examine the antitumor effect of direct in vivo gene transfer of murine interleukin 12 (IL-12) and B7-1 into tumors, we developed an adenovirus (Ad) vector, AdIL12-B7-1, that encodes the two IL-12 subunits in early region1 (El) and the B7-1 gene in E3 under control of the murine cytomegalovirus promoter, This vector expressed high levels of IL-12 and B7-1 ininfected murine and human cell lines and in primary murine tumor cells, In mice bearing tumors derived from a transgenic mouse mammary adenocarcinoma, a single intratumoral injection with a low dose (2.5 x 10(7) pfu/mouse) of AdIL12-B7-1 mediated complete regression in 70% of treated animals, By contrast, administration of a similar dose of recombinant virus encoding IL-12 or B7-1 alone resulted in only a delay in tumor growth, Interestingly, coinjection of two different viruses expressing either IL-12 or B7-1 induced complete tumor regression in only 30% of animals treated at this dose, Significantly, cured animals remained tumor free after rechallenge with fresh tumor cells, suggesting that protective immunity had been induced by treatment with AdIL12-B7-1,These results support the use of Ad vectors as a highly efficient delivery system for synergistically acting molecules and show that the combination of IL-12 and B7-1 within a single Ad vector might be a promising approach for in vivo cancer therapy.

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Documento generato il 06/07/20 alle ore 07:36:47