¹Center for Applied Medical Research, School of Medicine, and University Clinic, University of Navarra, Avenida Pio XII, 55, 31008 Pamplona, Spain

Correspondence: Ignacio Melero, E-mail: imelero@unav.es

^*These authors contributed equally to this work.

^†These authors share senior authorship.

Received 27 September 2005; Revised 26 January 2006; Accepted 14 February 2006.

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- and IFN- transcription from both plasmacytoid and myeloid mouse dendritic cells. Interestingly, IFN- and IFN-5 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- together with IFN-1 and IFN-5 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- 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- 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.