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

Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas
Authors: Melero, I. (Ignacio)
Duarte, M. (Marina)
Ruiz, J. (Juan)
Sangro, B. (Bruno)
Galofre, J.C. (Juan Carlos)
Mazzolini, G. (Guillermo)
Bustos, M. (Matilde)
Qian, C. (Cheng)
Prieto, J. (Jesús)
Keywords: Dendritic cell
Interleukin-12
Colon cancer
Adenovirus
CTLs
Issue Date: 1999
Publisher: Nature Publishing Group
Publisher version: http://www.nature.com/gt/journal/v6/n10/full/3301010a.html
ISSN: 1476-5462
Citation: Melero I, Duarte M, Ruiz J, Sangro B, Galofre J, Mazzolini G, et al. Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas. Gene Ther 1999 Oct;6(10):1779-1784.
Abstract
Stimulation of the antitumor immune response by dendritic cells (DC) is critically dependent on their tightly regulated ability to produce interleukin-12 (IL-12). To enhance this effect artificially, bone marrow (BM)-derived DC were genetically engineered to produce high levels of functional IL-12 by ex vivo infection with a recombinant defective adenovirus (AdCMVIL-12). DC-expressing IL-12 injected into the malignant tissue eradicated 50-100% well established malignant nodules derived from the injection of two murine colon adenocarcinoma cell lines. Successful therapy was dependent on IL-12 transfection and was mediated only by syngeneic, but not allogeneic BM-derived DC, indicating that compatible antigen-presenting molecules were required. The antitumor effect was inhibited by in vivo depletion of CD8+ T cells and completely abrogated by simultaneous depletion with anti-CD4 and anti-CD8 mAbs. Mice which had undergone tumor regression remained immune to a rechallenge with tumor cells, showing the achievement of long-lasting systemic immunity that also was able to reject simultaneously induced concomitant untreated tumors. Tumor regression was associated with a detectable CTL response directed against tumor-specific antigens probably captured by DC artificially released inside tumor nodules. Our results open the possibility of similarly treating the corresponding human malignancies.
Permanent link: http://hdl.handle.net/10171/21741
Appears in Collections:DA - Medicina - Endocrinología - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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