These DC still have functional receptors and are exposed to the receptor antagonist laminarin in order to block them.

The cultured cells were subsequently pulsed with tumor antigen derived peptides (one per culture) at a concentration of 5 µg/mL in approximately 5 mL and at a cell density of 20 x 10e6/mL for 1 h.

DC based vaccines expressing the tumor antigens PSA or Her2/neu were produced in a pre-clinical work.

We have electroporated these DC with melanoma antigen RNA for a cross-presentation study and showed that they express the proteins ex vivo and in vivo.

DC exosomes along with various TLR ligands or cytokines such as IL-2 or alpha IFN were used to promote Mart-1 specific T cell priming and/or NK cell triggering in HHD2 mice. We demonstrated that only TLR3 and 9 ligation is able to induce CTL priming in vivo. However, exosomes in the absence of adjuvants can induce NK cell activation.

An HSV vector expressing full length tyrosinase, gp100 and MART-1 was used to transduce DC from melanoma patients which were then to be used for vaccination.

Using pharmacological inhibitors, or macrophages and DC from mice carrying a null mutation in MAP kinase signalling molecule(s), we have evidence for a role of certain MAP kinases in the regulation of IL-10 and IL-12, IFN-gamma production.

We used dendritic cells loaded with anti-DEC205-antigen constructs, consisting of a single-chain variable fragment (scFv) directed against DEC-205, genetically linked to different parts of the MAGE-A3 model antigen (i.e. the KKl and EVDPIGHLY peptides), in a study to compare antigen-loading strategies.

DC pulsed with tumor antigens were evaluated for their immunotherapy potential in EG7-OVA and P815 tumor models. Depletion of natural regulatory T cells in tumor bearing mice resulted in rejection of P815 cells, but not EG7-OVA, suggesting that regulatory T cells have a stronger impact on immune responses against weakly immunogenic or auto-antigen (P1A).

Attenuated Expression of A20 Markedly Increases the Efficacy of Double Stranded RNA-Activated Dendritic Cells as an Anti-Cancer Vaccine A20 is a zinc finger protein with ubiquitine-modifying activity. It has been described that A20 negatively regulates signaling induced by the tumor necrosis factor receptor and toll like receptor (TLR) family in a number of cell types, including mouse bone marrow-derived dendritic cells (DCs). However, the expression and effect of A20 in activated monocyte-derived DCs have not been previously evaluated. We report that DC...

This DC vaccine was produced from matured DC (matured using TNF alpha, IFN alpha and PGE2) which were subsequently transfected with CD40L-encoding RNA and tumor RNA.

Autologous dendritic cells are loaded with apoptotic leukemic cells from patients with B-CLL to be used as vaccine in patients with chronic lymphocytic leukemia. Preliminary data from a clinical study indicate reduction of circulating tumor cells. No adverse effects have been observed.

This DC vaccine was produced from the Leukapheresis product, after elutriation, of a metastatic lesion of stage III/IV melanoma patients.

Three patients were enrolled in a clinical trial and DC vaccine was produced. The DC vaccine was administered into irradiated tumours in RCC of one patient only due to cancer progression in the other two patients. The patient treated is in complete remission 6 months after treatment.

The receptors of these DC were blocked by addition of laminarin, mannan and chitin.

This vaccine was used for RCC patients who were deficient in T cell IFN-gamma and IL-2 production pre-vaccination.

We showed that, in the absence of adjuvants, DEX mediate potent antigen dependent-antitumor effects against preestablished tumors in mice pretreated with immunopotentiating dosing of cyclophosphamide (CTX). CTX could i) abolish the suppressive function of CD4+CD25+Foxp3+ regulatory T cells (Treg), ii) markedly enhance the magnitude of secondary but not primary CTL responsesinduced by DEX vaccines, iii) synergize with DEX in therapy but not prophylaxis tumor models.

Constructs for fusion proteins of the DC specific receptor DC-SIGN fused to GFP have been completed and tested.

We also show that DCs derived from ashen mice, which are defective for the small GTPase Rab27a, fail to cross present antigens efficiently, due to increased phagosome acidification and antigen degradation. This defect in Rab27a-deficient DCs results from the impaired recruitment to phagosomes of the NOX2 membrane components. Therefore phagosomal alkalinization by NOX2 is controlled by Rab27a, and is required for efficient cross presentation in DCs.

DCs pre-loaded in vitro with ICs are at least 1000-fold more potent than ICs injected directly into mice or DCs loaded with the same amount of non-complexed protein. FcgammaRs on DCs were required for efficient priming of Ag-specific CD8+ cells in vivo and induction of tumor protection.