This patient has received 9 vaccines with peptides only in a randomized trial to receive immunizations either with I3 DC (DC generated with interferon-beta and interleukin-3) or with G4 DC (DC generated with GM-CSF and IL-4). Up to now, in Cycle 3, immunizations have been continued with peptide-only injections of all 9 peptides except Tyrosinase at 12 weeks intervals. For the continuation of the vaccinations the clinicians have decided to inject the patient at 6 months intervals. The patient who clinically showed Partial Response at the end of cycle 1 is curre...

We have finalized analysis of the receptors on DCs responsible for capture of exosomes secreted by mature DCs. We have shown that expression of LFA-1, but not of Mac-1, integrin, on DCs is required for capture of ICAM-1-bearing exosomes.

We have investigated the respective role of IL-10 and IDO, both required for Th1 suppression in this model. As IL-10 has been shown to indirectly dampen Th1 responses through the inhibition of IL-12 production by antigen-presenting-cells, we monitored mRNA expression specific for the inducible chain IL-12 p35 in lymph nodes draining the site of injection or in mesenteric lymph nodes of mice instilled intra-colonically with TNBS. Our results clearly show that IL-12 production early after the onset of the response was unaffected by anti-CTLA-4 treatment. By cont...

IDO appears critical for the regulation of TNBS colitis upon CTLA-4 engagement, as the beneficial effect of anti-CTLA-4 treatment was lost in IDO-deficient mice. By contrast, the absence of IDO did not alter the course of inflammation in mice injected with TNBS only, an unexpected finding which suggests that IDO-dependent counter-regulation requires other factors/cells in addition to IDO production and T cell activation by TNBS.

IFN alpha was used in a DC maturation process with the final aim to produce a DC vaccine.

We performed co-cultures of IFN-DCs with zoledronate-stimulated gamma delta T lymphocytes. Gamma delta T-cell activation, as demonstrated by their up-modulation of activation marker expression levels (e.g. CD25 and CD69), was observed. The studies demonstrated for the first time the existence of a bidirectional activating interaction between DCs and gamma delta T lymphocytes activated by aminobiphosphonates.

These K/O mice were studied with regard to responses to viral infections. We used the mouse pox virus Ectromelia and MVA-BN. Coinfection with MVA-BN and Ectromilia protected the IFNalpha receptor -/- mice. The data show that MVA-BN can induce potent innate immune responses able to control viral replication to allow the specific immune response to eliminate Ectromelia in immune deficient mice.

We identified a novel DC subset called IKDC producing IFNg and expressing TRAIL which can recognize and kill transformed tumor cells in vitro and in vivo. Cultures were generated of tumor cells with IKDC producing IFNg and expressing TRAIL which can recognize and kill transformed tumor cells in vitro and in vivo. IKDC generate long contacts and synapses with tumor cells and ultimately kill them within 4 hours.

We have investigated the respective role of IL-10 and IDO, both required for Th1 suppression in this model. As IL-10 has been shown to indirectly dampen Th1 responses through the inhibition of IL-12 production by antigen-presenting-cells, we monitored mRNA expression specific for the inducible chain IL-12 p35 in lymph nodes draining the site of injection or in mesenteric lymph nodes of mice instilled intra-colonically with TNBS. Our results clearly show that IL-12 production early after the onset of the response was unaffected by anti-CTLA-4 treatment. By cont...

It was shown that both IL-10 as well as IL-12 production is dependent on the signalling adaptor molecules either MyD88 or TRIF, respectively in response to CpG, LPS or PolyIC.

It was shown that both IL-10 as well as IL-12 production is dependent on the signalling adaptor molecules either MyD88 or TRIF, respectively in response to CpG, LPS or PolyIC.

Monocytes were transferred into culture bags by sterile welding and cultured for 5 days in serum free medium (CellGro, Cell Genix) in the presence of 100 ng/mL GM-CSF (Leukine, Berlex) and 20 ng/mL IL-4 (Cell Genix).

These DC were generated by culturing enriched monocytes for 5 days.

These DC were used in a maturation step for subsequent production of a DC vaccine.

These cells acquire a mature phenotype along with an enhanced secretion of several cytokines/chemokines. Moreover, these DCs are very potent in inducing naive CD4(+) T cells to differentiate into interferon-gamma (IFN-gamma)-secreting type 1 T helper (Th1) cells.

These cells do not acquire a mature phenotype and do not lead to an enhanced secretion of several cytokines/chemokines.

Antigen-specific CD4+ T cells were followed in these immunized individuals using generated peptide-MHC class II multimers.

By immunizing mice with ovalbumin-conjugated anti-Siglec-H Ab in the presence of CpG, we demonstrated generation of antigen-specific CD8 T cells in vivo.

ImmunoVexHSV2 is a product for the prevention of infectious disease, it is a vaccine for genital herpes. In preclinical studies, ImmunoVex HSV2 completely prevents disease and invokes a powerful immune response.

These DC were used to elicit CTL responses in a mouse model.