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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 >

Recombinant adenoviral vectors turn on the type I interferon system without inhibition of transgene expression and viral replication
Authors: Huarte, E. (Eduardo)
Larrea, E. (Esther)
Hernandez-Alcoceba, R. (Rubén)
Alfaro, C. (Carlos)
Murillo, O. (Oihana)
Arina, A. (Ainhoa)
Tirapu, I. (Íñigo)
Azpilicueta, A. (Arantza)
Hervas-Stubbs, S. (Sandra)
Bortolanza, S. (Sergia)
Perez-Gracia, J.L. (José Luis)
Civeira, M.P. (María Pilar)
Prieto, J. (Jesús)
Riezu-Boj, J.I. (José Ignacio)
Melero, I. (Ignacio)
Keywords: Interferon-alpha
Interferon-beta
Dendritic cell
Plasmacytoid dendritic cell
Adenovirus
Gene therapy
Immunotherapy
Issue Date: 2006
Publisher: Nature Publishing Group
Publisher version: http://www.nature.com/mt/journal/v14/n1/full/mt20061275a.html
ISSN: 1525-0024
Citation: Huarte E, Larrea E, Hernandez-Alcoceba R, Alfaro C, Murillo O, Arina A, et al. Recombinant adenoviral vectors turn on the type I interferon system without inhibition of transgene expression and viral replication. Mol Ther 2006 Jul;14(1):129-138.
Abstract
Recombinant adenovirus administration gives rise to transgene-independent effects caused by the ability of the vector to activate innate immunity mechanisms. We show that recombinant adenoviruses encoding reporter genes trigger IFN-alpha and IFN-beta transcription from both plasmacytoid and myeloid mouse dendritic cells. Interestingly, IFN-beta and IFN-alpha5 are the predominant transcribed type I IFN genes both in vitro and in vivo. In human peripheral blood leukocytes type I IFNs are induced by adenoviral vectors, with a preponderance of IFN-beta together with IFN-alpha1 and IFN-alpha5 subtypes. Accordingly, functional type I IFN is readily detected in serum samples from human cancer patients who have been treated intratumorally with a recombinant adenovirus encoding thymidine kinase. Despite inducing functional IFN-alpha release in both mice and humans, gene transfer by recombinant adenoviruses is not interfered with by type I IFNs either in vitro or in vivo. Moreover, IFN-alpha does not impair replication of wild-type adenovirus. As a consequence, cancer gene therapy strategies with defective or replicative-competent adenoviruses are not expected to be hampered by the effect of the type I IFNs induced by the vector itself. However, type I IFN might modulate antitumor and antiadenoviral immune responses and thus influence the outcome of gene immunotherapy.
Permanent link: http://hdl.handle.net/10171/20417
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Inmunología clínica - Artículos de revista
DA - CUN - Medicina interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Terapia génica del cáncer - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Virología - 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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