This vaccine consists of G4-DC loaded with 8 different peptides. It was tested in a trial in small cohorts of patients (3-9) who were vaccinated with differently composed DC-vaccines.

We have conducted a phase I long peptide vaccination trial with p53 peptides in Montanide adjuvant in patients with colorectal cancer or ovarium cancer.

These ovarian carcinoma patients are treated with a vaccine composed by autologous DCs pulsed with apoptotic autologous ovarian carcinoma cells.

This PGE2 was used in a DC maturation process with the final aim to produce a DC vaccine.

The patients were vaccinated with a vaccine composed by autologous DCs pulsed with apoptotic allogenic prostate carcinoma cell line LNCap.

We set an in vitro system to study ex-vivo responses able to detect fona fide in vivo primed CD4+ T cells. We investigated spontaneous CD4+ T cell responses to these antigens in normal donors and in patients with high-grade cervical lesions, pancreas adenocarcinoma and advanced melanoma. The antigens were: i) the E6 and E7 proteins of human papilloma viruses, ii) the carcinoembryonic antigen (CEA) and iii) the tumour specific antigen MAGE-A3.

We set an in vitro system to study ex-vivo responses able to detect fona fide in vivo primed CD4+ T cells. We investigated spontaneous CD4+ T cell responses to these antigens in normal donors and in patients with high-grade cervical lesions, pancreas adenocarcinoma and advanced melanoma. The antigens were: i) the E6 and E7 proteins of human papilloma viruses, ii) the carcinoembryonic antigen (CEA) and iii) the tumour specific antigen MAGE-A3.

We set an in vitro system to study ex-vivo responses able to detect fona fide in vivo primed CD4+ T cells. We investigated spontaneous CD4+ T cell responses to these antigens in normal donors and in patients with high-grade cervical lesions, pancreas adenocarcinoma and advanced melanoma. The antigens were: i) the E6 and E7 proteins of human papilloma viruses, ii) the carcinoembryonic antigen (CEA) and iii) the tumour specific antigen MAGE-A3.

These patients were treated in a long peptide trial. Analysis of the local immune response demonstrated the presence of HPV16-specific Th1/Th2 cells infiltrating the vaccination site and the VIN lesion after vaccination. 5 out of 20 patients showed complete clearance of all VIN III disease and in 4 of these this was also associated with complete clearance of HPV16 virus.

Perforine expressing T cells were observed in human Hemato-Lymphoid System Rag2-/-gc-/- mice after being infected with EBV and mounting an immune response. They infiltrated in B cell infected areas in lymphoid organs in situ.

PBMC are Leukapheresis derived and are loaded with peptide pools, each consisting of 10 15-mers, which overlap with 11 aminoacids.

We have analyzed the uptake, conservation and cross-presentation of the model antigen OVA after Fc receptor-mediated uptake by DC. We found that MHC class I presentation is relatively short-lived in contrast to MHC class II. However, CD8 cross-priming capacity of OVA-loaded DC was functionally retained for many days, while peptide-pulsed DC had lost their priming capacity after 24 hours.

We set an in vitro system to study ex-vivo responses able to detect fona fide in vivo primed CD4+ T cells. We investigated spontaneous CD4+ T cell responses to these antigens in normal donors and in patients with high-grade cervical lesions, pancreas adenocarcinoma and advanced melanoma. The antigens used were: i) the E6 and E7 proteins of human papilloma viruses, ii) the carcinoembryonic antigen (CEA) and iii) the tumour specific antigen MAGE-A3.

The effect of environmental factors on development of high affinity CTL was investigated using a system whereby OT-1 cells were primed in vitro by engineered APC. After a 20 h priming phase, CTL were transferred to recipient mice that were either naïve, or had been injected with activated dendritic cells one day earlier, thus creating a reactive lymph node.

The normal donors were studied for effector vs. memory T cell responses.

The expression and function of these murine FcgammaR in CD11c+CD11b-B220+ plasmacytoid DCs (pDCs) was investigated. pDCs express mostly FcgammaRIIB while the expression of FcgammaRI and FcgammaRIII is only detected by RT-PCR at low but significant level. Moreover, the ITAM-containing intracellular chain associated to FcgammaRI and FcgammaRIII is strongly expressed in pDCs as detected by biochemical assay.

When we tested in therapeutic tumor experiments with OVA+ melanoma cells, direct administration of lentiviral vectors slowed down tumor growth to a comparable extent with the highest dose of ex vivo transduced DC.

The group completed the measurements of murine dendritic cell subsets and established an in-depth proteomic map of them. These preliminary results show more than 4500 identified proteins in each subset. All of the known markers like CD11c, CD11b, DEC-205, Langerin, etc. were found according to their differential expression pattern.

The role of IL-10 in the immune response to MTb was studied. We have identified that IL-10 plays an early and transient role in the control of the immune response to MTb and now show that this involves enhanced migration of IFNgamma producing CD4+ and CD8+ T cells into the lung rather than enhanced mycobacterial killing. The effects are accompanied by enhanced G-CSF, GM-CSF, TNF, IL-6 and IL-17 levels although the enhanced clearance of bacilli in IL-10 deficient mice we now show is independent of IL-17.

Injection of lentiviral vectors activated OVA-specific CD4+ T cells and this CD4 help was shown to be necessary for an adequate primary and memory CTL response.