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Titolo:
Regression of human mammary adenocarcinoma by systemic administration of arecombinant gene encoding the hFlex-TRAIL fusion protein
Autore:
Wu, XF; He, YK; Falo, LD; Hui, KM; Huang, L;
Indirizzi:
Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 cogenet, Pittsburgh, PA 15261 USA Univ Pittsburgh, Inst Canc, Dept Dermatol, Pittsburgh, PA 15216 USA Univ Pittsburgh Pittsburgh PA USA 15216 ermatol, Pittsburgh, PA 15216 USA Natl Canc Ctr, Div Cell & Mol Biol, Singapore 169610, Singapore Natl Canc Ctr Singapore Singapore 169610 ol, Singapore 169610, Singapore
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 3, volume: 3, anno: 2001,
pagine: 368 - 374
SICI:
1525-0016(200103)3:3<368:ROHMAB>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; APOPTOSIS-INDUCING LIGAND; FLT3 LIGAND; IN-VIVO; DENDRITIC CELLS; PLASMID DNA; TNF FAMILY; T-CELLS; RECEPTORS; EXPRESSION;
Keywords:
TRAIL; Flt3L (hFlex); fusion protein; isoleucine zipper; cancer gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Huang, L Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 Pittsburgh, PA 15261 USA
Citazione:
X.F. Wu et al., "Regression of human mammary adenocarcinoma by systemic administration of arecombinant gene encoding the hFlex-TRAIL fusion protein", MOL THER, 3(3), 2001, pp. 368-374

Abstract

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand, TRAIL, is a new member of the TNF family. It can specifically induce apoptosis in a variety of human tumors. To investigate the possibility of employing the TRAIL gene for systemic cancer therapy, we constructed a recombinant gene encoding the soluble form of the human Flt3L gene (h Flex) at the 5' end andthe human TRAIL gene at the 3' end. Such design allows the TRAIL gene product to be secreted into the body circulation. We have also demonstrated that the addition of an isoleucine zipper to the N-terminal of TRAIL greatly enhanced the trimerization of the fusion protein and dramatically increased its anti-tumor activity. The fusion protein reached the level of 16-38 mug/ml in the serum after a single administration of the recombinant gene by hydrodynamic-based gene delivery in mice. A high level of the fusion protein correlated with the regression of a human breast tumor established in SCID mice. No apparent toxicity was observed in the SCID mouse model. In addition, the fusion protein caused an expansion of the dendritic cell population in the C57BL/6 recipient mice, indicating that the hFlex component of the fusion protein was functional. Thus, the hFlex-TRAIL fusion protein may provide a novel approach, with the possible involvement of dendritic cell-mediated anti-cancer immunity, for the treatment of TRAIL-sensitive tumors.

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Documento generato il 14/07/20 alle ore 10:17:00