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Titolo:
Enhancement of antitumor immunity against B16 melanoma tumor using genetically modified dendritic cells to produce cytokines
Autore:
Akiyama, Y; Watanabe, M; Maruyama, K; Ruscetti, FW; Wiltrout, RH; Yamaguchi, K;
Indirizzi:
Natl Canc Ctr, Res Inst, Div Growth Factor, Chuo Ku, Tokyo 104, Japan NatlCanc Ctr Tokyo Japan 104 v Growth Factor, Chuo Ku, Tokyo 104, Japan NCI, Expt Therapeut Sect, Expt Immunol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA NCI Frederick MD USA 21701 ck Canc Res & Dev Ctr, Frederick, MD 21701 USA NCI, Lab Leukocyte Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21701USA NCI Frederick MD USA 21701 ick Canc Res & Dev Ctr, Frederick, MD 21701USA
Titolo Testata:
GENE THERAPY
fascicolo: 24, volume: 7, anno: 2000,
pagine: 2113 - 2121
SICI:
0969-7128(200012)7:24<2113:EOAIAB>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
RESPONSES IN-VITRO; T-CELLS; INTRATUMORAL INJECTION; CARCINOEMBRYONIC ANTIGEN; IFN-GAMMA; PHASE-I; INTERLEUKIN-12; PEPTIDE; IL-12; VIVO;
Keywords:
interleukin (IL)-12; malignant melanoma; genetically modified dendritic cells (DC); intratumoral injection;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Akiyama, Y Natl Canc Ctr, Res Inst, Div Growth Factor, Chuo Ku, 5-1-1 Tsukiji, Tokyo 104, Japan Natl Canc Ctr 5-1-1 Tsukiji Tokyo Japan 104 , Tokyo 104, Japan
Citazione:
Y. Akiyama et al., "Enhancement of antitumor immunity against B16 melanoma tumor using genetically modified dendritic cells to produce cytokines", GENE THER, 7(24), 2000, pp. 2113-2121

Abstract

Dendritic cells (DC) that have been genetically modified to express cytokine genes may be novel tools for inducing antitumor immune responses. In thepresent study, the pMX retroviral vector was modified to express the mouseIL-2 (mlL-2pMX) and mouse IL-12 (mlL-12pMX) genes. Supernatants from 293 cells transfected with pMX retroviral vectors were harvested and used to transduce mouse lin bone marrow (BM) progenitor cells. After 48 h co-culture with pseudotype retrovirus, BM cells were cultured for 12 days in the presence of mGM-CSF, mSCF and mTNF-alpha to obtain a DC-enriched fraction. Flow cytometric analysis showed that GFP protein expression in these cultures was20-40% and that 40-50% of the cultured BM cells were positive for the DC marker, DEC205. About 60% of cells sorted for DEC205 also expressed GFP. Thesupernatants of DC-mlL-2 and DC-mlL-12 cultured for 48 h contained 5.2 +/-0.15 and 33.9 +/- 2.6 ng cytokine protein per milliliter, respectively. Intratumoral injection of DC-mlL-2 or DC-mlL-12 on days 8 and 15 after the intradermal injection of 1 x 10(5) B16F10 cells, resulted in a significant reduction in tumor size by day 21, as compared with mice treated with unmodified DC or DC-GFP. Longer term analysis as assessed at day 42 revealed that B16 tumor-bearing mice treated with cytokine gene-modified DC survived significantly longer than mice from other groups. Spleen cells obtained from DC-treated mice were specifically sensitized for the generation of CTL by subsequent restimulation with gene-modified DC. These results suggested that DC genetically modified to express IL-2 or IL-12 can induce potent antitumorresponses against well-established, poorly immunogenic B16F10 tumors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 01:43:27