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Titolo:
Antitumor efficacy of a human interleukin-12 expression plasmid demonstrated in a human peripheral blood leukocyte/human lung tumor xenograft SCID mouse model
Autore:
Hess, SD; Egilmez, NK; Shiroko, J; Bankert, RB;
Indirizzi:
Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA Roswell Pk Canc Inst Buffalo NY USA 14263 Immunol, Buffalo, NY 14263 USA Takayama Red Cross Hosp, Dept Internal Med, Gifu, Japan Takayama Red CrossHosp Gifu Japan Hosp, Dept Internal Med, Gifu, Japan
Titolo Testata:
CANCER GENE THERAPY
fascicolo: 5, volume: 8, anno: 2001,
pagine: 371 - 377
SICI:
0929-1903(200105)8:5<371:AEOAHI>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
COMBINED IMMUNODEFICIENT MICE; AUTOLOGOUS MELANOMA-CELLS; BIODEGRADABLE MICROSPHERES; GENE-THERAPY; LONG-TERM; VACCINATION; SUPPRESSION; LYMPHOCYTES; ELIMINATION; REGRESSION;
Keywords:
interleukin-12; tumor; cancer immunotherapy; human; SCID mouse;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Egilmez, NK Roswell Pk Canc Inst, Dept Immunol, Elm & Carlton St, Buffalo,NY 14263 USA Roswell Pk Canc Inst Elm & Carlton St Buffalo NY USA 14263 USA
Citazione:
S.D. Hess et al., "Antitumor efficacy of a human interleukin-12 expression plasmid demonstrated in a human peripheral blood leukocyte/human lung tumor xenograft SCID mouse model", CANC GENE T, 8(5), 2001, pp. 371-377

Abstract

Genes encoding the p35 and p40 subunits of human interleukin-12 (IL-12) and the bacterial aminoglycoside phosphotransferase were cloned into a mammalian expression plasmid. The resultant plasmid, pCMVIL-12neo, was used to transfect human lung tumor cell lines in vitro. Stably transfected subclones were generated and found to secrete human IL-12 for at least 10 days following a lethal dose of gamma -radiation. The ability of the IL-12-producing tumor eel Is to promote an antitumor response in vivo was evaluated in SCID mice co-engrafted subcutaneously with human peripheral blood lymphocytes (PBLs) and viable human lung tumor cells (SCID-Winn assay). Using this model system, it was established that IL-12 released locally into tumors by irradiated IL-12-transfected cells activated the human PBL and promoted their ability to suppress tumor development in a dose-dependent fashion. PBL subsetdepletion studies revealed that the antitumor effect promoted by the IL-12-modified cells was dependent on the presence of human CD8(+) T cells and, to a lesser extent, human CD56(+) natural killer cells within the xenograft. We conclude that (a) irradiated human lung tumor cells genetically modified with pCMVIL-12neo secrete bioactive human IL-12 at concentrations sufficient to promote a human lymphocyte-mediated antitumor response in the microenvironment of the xenograft, and (b) that the SCID-Winn assay provides a useful model for the preclinical evaluation of cytokine-based human immunotherapy protocols.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 22:33:44