This patient is undergoing i.v. application of indium labelled E/L-S DC (without antigen loading) in a study of DC migration.

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.

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.

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

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

Tumor growth is supported by tumor stroma, such as tumor associated macrophages (TAM) and tumor associated dendritic cells (TADC). We have recently reported that TAM display massive nuclear localization of the p50 NF-kB inhibitory homodimer, which correlates with impaired inflammatory functions.The functional significance of this observation was demonstrated in p50 NF-kB deficient mice, which displayed tumor growth inhibition.

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

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 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.

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 animal(s) were immunized in vivo with in vitro matured DC and / or treated using a maturation signal.

We have immunized mice with human DC derived-exosomes and generated hybridomas that produce antibodies recognizing at least the human exosomes.

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).

4 metastatic melanoma patients were actively vaccinated and additional injections were performed in disease free patients, in patients with stable disease or with slowly progressive disease.

These patients are involved in a phase II clinical trial for melanoma and are treated with OncoVexGMCSF. Data so far indicates that OncoVex can destroy both injected and un-injected melanoma deposits. The trial is still in progress.

The melanoma patients were vaccinated with a MAGE-A3 peptide presented by HLA-A1 without adjuvant, while other melanoma patients were vaccinated with ALVAC canarypox virus containing a MAGE-A3 minigene, or peptide-pulsed dendritic cells (DC). There was a correlation between tumor regression and detection of anti-MAGE-3.A1 CTL responses.

Some melanoma patients were vaccinated with the MAGE-A3, gp100, NA17 and tyrosinase peptides presented by HLA-A2 plus the montanide adjuvant, while others were vaccinated with the peptides without the adjuvant or with ALVAC canarypox virus (containing a MAGE-A3 minigene) viral vectors. There was a correlation between tumor regression and detection of anti-MAGE-3.A1 CTL responses.