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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12
Authors: Mazzolini, G. (Guillermo)
Qian, C. (Cheng)
Xie, X. (Xiaoming)
Sun, Y. (Yonglian)
Lasarte, J.J. (Juan José)
Drozdzik, M. (Marek)
Prieto, J. (Jesús)
Keywords: Gene therapy
Adenovirus
Interleukin-12
Colon cancer
Animal mode
Cytotoxicity
Issue Date: 1999
Publisher: Nature Publishing Group
Publisher version: http://www.nature.com/cgt/journal/v6/n6/abs/7700072a.html
ISSN: 1476-5500
Citation: Mazzolini G, Qian C, Xie X, Sun Y, Lasarte JJ, Drozdzik M, et al. Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12. Cancer Gene Ther 1999 Nov-Dec;6(6):514-522.
Abstract
Interleukin-12 (IL-12) has been shown to possess potent immunoregulatory and antitumoral effects. We have evaluated the anti-oncogenic potential and the mechanisms of the antitumoral effect of in vivo adenovirus-mediated transfer of IL-12 gene in a murine model of colon cancer. AdCMVIL-12 was constructed to permit coordinated production of p40 and p35 subunits of IL-12 gene to obtain the maximum IL-12 bioactivity. Infection of murine colon cancer CT-26 cells in vitro with AdCMVIL-12 resulted in the production of high levels of IL-12. In vivo gene therapy of colon cancer nodules by intratumoral injection of AdCMVIL-12 induced a local increase in IL-12 and interferon-gamma levels and a complete regression of the tumor in 26 of 34 (76%) mice. Tumor disappeared between days 7 and 10 after vector administration. The antitumoral effect was mediated by CD8+ T cells and was associated with the generation of cytotoxic T lymphocytes against colon cancer cells. Animals that eliminated the tumor were protected against a second administration of neoplastic cells. Treatment with AdCMVIL-12 of one tumor nodule also caused regression of established tumors at distant sites. These data demonstrate that AdCMVIL-12 is a useful therapeutic tool for established colon cancer in mice and should be considered for application in humans.
Permanent link: http://hdl.handle.net/10171/21724
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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