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.

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...

These patients received multipeptide loaded cytokine matured moDC + prior Treg elimination by 3x ONTAK treatment [5µg/kg]; first phase of DERMA-ER-DC 05 trial.

These mice were used to study « in vivo » responses to Ags. We studied the kinetics of effector genes expression and association in TCR-Tg CD8 cells responding to the male antigen and to Listeria-OVA.

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.

These patients are taking part in a clinical study. They are patients that are successfully treated with highly active anti-retroviral therapy (HAART) with no measurable viral load AND have a cryopreserved infectious plasma sample that was drawn immediately prior to initiation of HAART. They are administered 4 monthly doses of the Arcelis product.

This patient has received 9 vaccines with peptides 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). Up to now, in Cycle 3, immunizations have been continued with peptide-only injections of all 9 peptides except Tyrosinase at 12 weeks intervals. For the continuation of the vaccinations the clinicians have decided to inject the patient at 6 months intervals. The patient who clinically showed Partial Response at the end of cycle 1 is curre...

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.

The patients were vaccinated with 4 peptides (MAGE-A3, gp100, NA17 and tyrosinase) presented by HLA-A2. We measured responses to these peptides injected with Montanide, but did not know whether the Montanide adjuvant was important for these T cell responses. Indeed, melanoma patients may mount spontaneous responses to these antigenic peptides. We therefore injected the same peptides without adjuvant, and no response was observed. We conclude that Montanide had a clear adjuvant effect for the CD8 T cell responses measured against these four peptides.

A vaccination trial with RNA transfected autologous DC was done with overlapping peptides covering the whole protein sequence of the tumor antigens MageA3, MelanA and Survivin. With this approach we monitored the immune responses of 8 vaccinated patients and of more than 15 other stage IV melanoma patients.

77 patients have been enrolled in two Phase III trials from 2 institutions testing dosing or duration of IM administration (EORTC 62005 and BFR14 trials).

An HIV infected individuals stable under HAART study has been initiated. These patients are being vaccinated with cytokine cocktail matured DCs electroporated with mRNA encoding Tat, Rev and Nef. The cDNA’s encoding these early expressed HIV antigens have been human codon optimized and modified with lysosomal targeting sequences. So far, 17 patients have been included in the study.

These patients were treated with monocyte-derived DCs matured with inflammatory cytokines and subsequently electroporated with mRNA encoding 6 tumor-associated antigens.

Three groups of end stage cervical cancer patients (in total N=35) were subcutaneously vaccinated with HPV16 E6 combined with or separated from HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant, 4 times at three week intervals. Group 1 received 300 microgram per peptide at a single site, group 2 received 100 microgram per peptide of the E6 peptides in one limb, and 300 microgram per peptide of the E7 peptides in a second limb. Group 3 received separate injections of E6 and E7 peptides, each at a dose of 50 micrograms per peptide. The primary endpo...

The B-CLL patients were vaccinated with autologous, apoptotic, leukemic cells (Apo-DC). The first cohort of patients received the vaccine without additional adjuvants, while the next cohort of 5 patients who receive the vaccine with GM-CSF as an adjuvant. Clinical trial on vaccination of B-CLL patients with autologous, apoptotic, leukemic cells (Apo-DC), progressed further in 2007. Cohort 1 with the vaccine alone and cohort 2 (5 patients) combining the vaccine together with GM-CSF as an adjuvant has finished accrual and all patients in these two cohorts have ...

RCC subjects were deficient in T cell IFN-gamma and IL-2 production pre-vaccination. Their response to DC-based immunotherapy was evaluated.