Cytolysis of Adenovirus-Infected Murine Fibroblasts by IFN-γ-Primed Macrophages Is TNF- and Contact-Dependent

Ischemia/reperfusion injury-mediated down-regulation of adenovirus-mediated gene expression in a rat heart transplantation model is inhibited by co-application of a TNFRp55-Ig chimeric construct

“…22,23 However, in several cell lineages (eg mature macrophages) TNF-␣ inhibits the hCMV-IE promoter activity, although NFB activation is also observed in those cells, 5,23 suggesting the involvement of negative regulatory elements in response to TNF-␣ in several cell types. Our data presented here and the observations by others 5,7 suggest that this inhibitory effect by TNF-␣ on the hCMV-IE promoter activity seems to play a major role following in vivo gene transfer.…”

“…Several data suggest that elimination of the Ad-transduced cells by the specific antiviral immune response is not the only reason for the down-regulation of the gene of interest expression. Our results presented here and the results of other groups 5,6,7,21 indicate that the viral promoters used in almost all gene therapy vectors owing to their strong transcriptional activity in vitro are sensitive to cytokines during inflammatory responses in vivo. This might be a major hindrance for the application of conventional gene therapy vectors where transgene expression is controlled by the hCMV-IE promoter.…”

“…7 Recently it has been shown that the blockade of TNF-␣ increased reporter gene expression after intranasal and intravenous Ad application into the lung and liver, suggesting the in vivo relevance of the cytokine-mediated control of hCMV-IE promoter-driven gene expression. 8,9 Gene therapy with Ad vectors may be a useful approach in the transplant setting.…”

Macrophage depletion increases the safety, efficacy and persistence of adenovirus-mediated gene transfer in vivo

“…[29][30][31][32] Furthermore, at least one recent study has demonstrated that macrophage controls. Many previous studies have documented the role of CTL in the elimination of virally transduced hepadepletion causes a greater than 95% reduction in the levels of IL-1␤, IL-6, IL-10 and IL-12 (p40) mRNA that are tocytes.…”

Replication-selective adenoviruses as oncolytic agents

“…Replication amplifies the input dose of the oncolytic virus and helps spread the agent to adjacent tumor cells (9). In addition, adenoviral infection may generate an antitumoral immune response (10)(11)(12). Given the favorable attributes of both therapeutic genes and replicationcompetent viral approaches, it is likely that the best clinical success will eventually be achieved with adenoviruses armed with therapeutic genes, used to complement standard surgical, radio-, and chemotherapeutic approaches.…”