Recently the high transfection potential of the cationic polyfold increased transfection efficiency. This activity depends mer polyethylenimine (PEI) was described (Boussif O et al. on ligand-receptor interaction and was observed also at Proc Natl Acad Sci USA 1995; 92: 7297-7301

The role of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) in down-regulating human alloresponses has recently been controversially debated. We here demonstrate that human monocyte-derived dendritic cells (mDCs) can be endowed with sustained IDO competence in vitro by 48-hour activation with lipopolysaccharide (LPS) and interferon-gamma (IFN-␥). IFN-␥ also amplified proinflammatory cytokine secretion during activation. Yet, on reculture after activation cytokine production ceased, whereas IDO enzymatic activity IntroductionIndoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan catabolism, has attracted attention for its proposed role in tolerance induction. 1,2 IDO, when expressed in antigen presenting cells (APCs), such as dendritic cells (DCs), establishes a microenvironment that at the DC/T-cell interface is depleted of tryptophan and enriched with tryptophan metabolites. Because of this alteration of the intercellular microenvironment, IDO activity has been suggested to impair T-cell responses. 3,4 The mechanisms of IDO-mediated inhibition include that T cells stimulated under tryptophan-depleted conditions are impaired to undergo full cell cycle progression 3,5 and are susceptible to apoptotic cell death. 6,7 Furthermore, it has been reported that IDO-expressing DCs can expand naturally occurring regulatory T cells. 8 In a murine model Fallarino et al 9 have shown that IDO activity supported the generation of adaptive regulatory T cells. Likewise, human IDOexpressing tumor cells have been reported to induce CD4 ϩ CD25 ϩ regulatory T cells. 10 Most recently, the previously recognized immunoregulatory activity of human plasmacytoid DCs has been related to IDO activity. 11 Thus, IDO-mediated down-regulation of T-cell responses has been suggested to be involved in a multitude of immunoregulatory processes, for example, pregnancy, 12 tumor growth, 13 and the induction of tolerance in transplantation (reviewed in Hainz et al 14 ).IDO expression is not a constitutive feature of human DCs in homeostatic immunologic conditions but requires induction. Among the multiple mediators of IDO induction (reviewed in Puccetti 15 ), interferon-␥ (IFN-␥) plays a prominent role. 16 IFN-␥ has generally been considered a prototypic proinflammatory cytokine (reviewed in Schoenborn and Wilson 17 ); compelling evidence, however, supports the ability of IFN-␥ to promote anti-inflammatory responses. [18][19][20] The ability of IFN-␥ to induce IDO has been suggested as a critical factor linked to this anti-inflammatory activity. 21,22 In our previous studies addressing possible mechanisms of the immunodeficient state after hematopoietic stem cell transplantation, 23 we found that monocytes after hematopoietic stem cell transplantation were particularly sensitive to respond to an exposure to IFN-␥ with an accelerated release of tryptophan metabolite kynurenine, and, thus, to turn into suppressor cells. This finding suggested the possibility that an augmented IDO activity in recipients of a hemat...

Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3–20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436–671 versus control: 568 days, 95% CI: 349–680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.

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