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.

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

These patients receive a DC vaccine composed by autologous DCs electroporated with mRNA encoding CD40L, CD70, caTLR4 and one tumorantigen (gp100, Tyrosinase, Mage-C2 or Mage-A3).

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.

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.

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 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...

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).

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

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.

This patient has received 6 vaccines with peptide 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). The patient received a sequence of six immunizations every two weeks, consisting of autologous dendritic cells loaded with the 8 HLA-A2 restricted peptides and MAGE.3-DP4 in Cycle 1. In Cycle 2, the patient received a sequence of three immunizations every six weeks, consisting of autologous dendritic cells loaded with the 8 HLA-A2 restric...

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.

These are RCC patients with clear cell histology, treated using the PME-CD40L DC product. At present, 6 of the 12 patients that have been restaged using RECIST criteria have less tumor burden that when they enrolled in the study (15 weeks earlier).

This patient experienced an outstanding response to immunotherapy. The patient received several adoptive T cell transfers and regressed from stage IV melanoma to a disease free state and has remained tumor free for several years.

DC-based vaccines that were given to these patients were combined with low dose IFN-alfa (3 x 10e6 U per wk). In a number of patients we observed vaccine-induced depigmentation and vitiligo.