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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 coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy
Authors: Narvaiza, I. (Íñigo)
Mazzolini, G. (Guillermo)
Barajas, M. (Miguel)
Duarte, M. (Marina)
Zaratiegui, M. (Mikel)
Qian, C. (Cheng)
Melero, I. (Ignacio)
Prieto, J. (Jesús)
Keywords: Adenoviridae/immunology
Antineoplastic Agents/immunology
Chemokines, CXC/immunology*
Interferon-gamma/immunology
Interleukin-12/immunology
Vaccines, DNA/immunology
Viral Vaccines/immunology
Issue Date: 2000
Publisher: American Association of Immunologist
Publisher version: http://www.jimmunol.org/content/164/6/3112
ISSN: 1550-6606
Citation: Narvaiza I, Mazzolini G, Barajas M, Duarte M, Zaratiegui M, Qian C, et al. Intratumoral coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy. J Immunol 2000 Mar 15;164(6):3112-3122.
Abstract
We have constructed a recombinant defective adenovirus that expresses functional murine IFN-gamma-inducible protein-10 (IP-10) chemokine (AdCMVIP-10). Injection of AdCMVIP-10 into s.c. tumor nodules derived from the CT26 murine colorectal adenocarcinoma cell line displayed some antitumor activity but it was not curative in most cases. Previous studies have shown that injection of similar s. c. CT26 tumor nodules with adenovirus-encoding IL-12 (AdCMVIL-12) induces tumor regression in nearly 70% of cases in association with generation of antitumor CTL activity. AdCMVIP-10 synergizes with the antitumor effect of suboptimal doses of AdCMVIL-12, reaching 100% of tumor eradication not only against injected, but also against distant noninjected tumor nodules. Colocalization of both adenoviruses at the same tumor nodule was required for the local and distant therapeutic effects. Importantly, intratumoral gene transfer with IL-12 and IP-10 generated a powerful tumor-specific CTL response in a synergistic fashion, while both CD4 and CD8 T cells appeared in the infiltrate of regressing tumors. Moreover, the antitumor activity of IP-10 plus IL-12 combined gene therapy was greatly diminished by simultaneous in vivo depletion of CD4+ and CD8+ T cells but was largely unaffected by single depletion of each T cell subset. An important role for NK cells was also suggested by asialo GM1 depletion experiments. From a clinical point of view, the effects of IP-10 permit one to lower the required gene transfer level of IL-12, thus preventing dose-dependent IL-12-mediated toxicity while improving the therapeutic efficacy of the elicited antitumor response.
Permanent link: http://hdl.handle.net/10171/21774
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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