Small cohorts of patients (3-9) were vaccinated with differently composed DC-vaccines: DC loaded with a single MAA-derived peptide (MAGE-3.A1 or -A2 or Na17.A2) or pulsed with 2 to 3 MAA-derived peptides (combinations of MAGE-3.A2, MAGE-C2.A2 or Na17.A2) or G4-DC loaded with 8 different peptides. An important conclusion that can be made from these pilot-observations is that the potential therapeutic effect of our DC-based MAA-vaccination approach does not occur instantly but is delayed by 8-12w following the first vaccination (i.e.12-16w after the isolation o...

Four patients are enrolled in a clinical trial for vaccination with DC loaded with apoptotic leukemic cells. A strong type I T cell response has been induced. Preliminary data also indicate reduction of circulating tumor cells. No adverse effects have been observed.

Three patients were enrolled in a clinical trial of a DC vaccine administered into irradiated tumours in RCC. However only this one patient received the vaccine due to cancer progression in the other two patients. The DC were labelled with 111In. The following patients will receive DC labelled with Endorem and the vaccine will be imaged with MRI. The patient treated is in complete remission 6 months after treatment.

An HLA-A2 positive healthy donor underwent leukapheresis with the aim to generate monocyte derived DC under GMP conditions.

These 70 patients were evaluated in the DERMA-ER-DC 04 clinical trial of DC-based therapy of melanoma patients (multipeptide loaded cytokine matured moDC +/- CD40L activation). The analysis for the first time showed a clinical correlation of induced immune responses as measured in the blood with outcome, as there have been so far statistically significantly less events in stage III patients showing good CTL reponses (IFN-y Elispot) to multiple class I and II peptides compared to low responders of the stage III cohort. Additional in vitro maturation of DC by CD...

We have attempted to identify the antigen-presenting cells (APCs) that are responsible for the development of immune tolerance in mice that have been breast-fed by antigen-exposed lactating mothers. Recent experiments performed in our laboratory have shown that the exposure of a mother to an airborne antigen during lactation impacts asthma development in their progeny. We found that airborne allergens were efficiently transferred from the mother to the neonate through the milk and that this transfer resulted in the development of antigen-specific tolerance.

Patients with stage III or stage IV melanoma who undergo surgical resection of a melanotic lesion. These patients are vaccinated with pulsed and thouroughly tested dendritic cell vaccine.

These patients undergo leukapheresis and later intradermal administration of the produced vaccine (V administrations of autologous dendritic cells generated from adherent peripheral blood monocytes and subject to quality controls - with eventual additional ones depending on clinical outcome).

These patients undergo leukapheresis and later intradermal administration of the produced vaccine (V administrations of autologous dendritic cells generated from adherent peripheral blood monocytes and subject to quality controls - with eventual additional ones depending on clinical outcome).

These are strains of Saccharomyces cerevisiae that were cultured and collected in different conditions: - different growth phase (exponential and stationary phase) - different growth media (standard and promoting pseudohyphal growth) - different cell form (spheroplast, spore and whole cell)

The mice were generated with the intention to elucidate in vivo DC developmental regions in steady state and inflammation in situ.

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 animals were used to test the combined effects of these cytokines on DC development in vivo.

We found a novel M-CSF dependent DC developmental pathway that is independent of Flt3L. These DC have unique characteristics and precursor origin. The cells can be found in vivo in Flt3L gene deleted (-/-) mice injected with recombinant M-CSF.

These HIV strains were used to infect Human Hemato-Lymphoid System Rag2gc-/- mice to closely resemble HIV infection in humans.

These HIV strains were used to infect Human Hemato-Lymphoid System Rag2gc-/- mice to closely resemble HIV infection in humans.

These mice were infected with both CXCR4 as well as CCR5 tropic HIV-1 strains. HIV causes a disseminated infection and spreads in all newly generated lymphoid tissues, thus closely resembling HIV infection in humans. We are now aiming to improve the recipient mouse background by co-transplanting human mesenchymal stroma cells, and by adding human cytokines as well as human MHC. Furthermore, we use the mice to evaluate targeted therapies directed at human immune system cells as T cells, B cells, and dendritic cells.

The mice were infected with EBV and mount an immune response (i.e. cytotoxic T cell proliferation, some control of EBV driven B cell proliferation, perforine and granzyme expressing T cell infiltration in B cell infected areas in lymphoid organs in situ), however, specific T cells could not be detected directly ex vivo by looking at the most common EBV derived/presented epitopes (tetramer staining). Some animals developed EBV induced B cell lymphoproliferative disease.

We established “human hemato-lymphoid-system mice” by transplanting human CD34+ cord blood cells into irradiated newborn Rag2-/-gc-/- mice, leading to de novo development of human B, T, and dendritic cells.