Our lead product for the treatment of cancer is OncoVex GMCSF. OncoVexGMCSF is completing a 50-patient Phase II clinical trial for the treatment of unresectable metastatic melanoma, as a monotherapy, in the second line/salvage therapy setting. Data so far indicates that OncoVex can destroy both injected and un-injected melanoma deposits. The trial is still in progress.

Data has been obtained on the BRAF/NRAS mutation status and expression of COX-2 and iNOS comparing their prognostic value for overall survival in stage III malignant melanoma. New prognostic markers for malignant melanoma are urgently needed. Inducible nitric oxide synthase (iNOS) and cyclooxygenase type 2 (COX-2) have been described to correlate with progression of melanoma. Moreover, activating mutations in BRAF/NRAS oncogenes are often detected in melanoma. We have examined the BRAF/NRAS mutation status and expression of COX-2 and iNOS to compare their progno...

We found that Indium111 labelled DC should not be loaded with tumor antigens if applied in patients, which may result in loss of specific immune responses and are testing this in-vivo. Analysis of DC migration in vivo in a first patient by i.v. application of indium labelled E/L-S DC (without antigen loading) is scheduled for March 2009. Data will become available.

A worldwide first randomized adjuvant trial in a subgroup of high risk melanoma patients (monosomy 3) using autologous DC transfected with amplified total tumor RNA derived from patients' uvea melanomas was to be started in 2009 and data will become available.

High-throughput data is available on tumour-associated antigen (TAA) specific T-cells in breast cancer patients using the Becton Dickinson Lyoplate™ technology. Therefore we have established multiparameter assessments of antigen-specific CD4+ and CD8+ T-cells enabling a simultaneous quantitative and qualitative analysis.

(This trial is expected for 2009 and data will become available.)

We have obtained data from a phase I long peptide vaccination trial with p53 peptides in Montanide adjuvant in patients with colorectal cancer or ovarium cancer. This vaccine was well tolerated and robust p53-specific T cell responses were induced. In the future we intend to combine the p53 vaccine with other cancer therapies such as chemotherapy.

In 2008 we have started a trial in patients with VIN3 disease (similar to the Phase I/II clinical trial on the use of long peptides plus adjuvant for end-stage cervical cancer or VIN patients), in which we are comparing the efficacy of this vaccine with or without local application at the vaccination site of the TLR ligand imiquimod (Aldara). Results and data will become available.

The study protocol that will be used for this trial has been reviewed by the local ethical committee and is now ready to be submitted to Läkemedelsverket, the Swedish regulatory authority for clinical trials. Upon approval by Swedish authorities we plan to include, treat and evaluate 10 patients during a period of one to two years. It will probably start in 2009 and data will become available.

The initiation of a multi partner trial is planned and data will be generated. The DC-THERA trial will compare the use of ‘TRI-MIX’ RNA in clinical trials that were already underway at each of the three centres (Nijmegen Medical School, Nijmegen; Friedrich-Alexander University, Erlangen; Vrije Universiteit Brussel, Brussels). It was decided that Friedrich-Alexander University, Erlangen, would apply for a licence to prepare GMP-grade ‘TRI-MIX’ RNA and subsequently supply this for all three centres. The multi-centre trial is a well-standardised, two-arm, m...

Data will become available on the safety, antitumoral immune response and DC migration in the organism in patients with advance renal cell carcinoma and melanoma from this trial using cellular immunotherapy with dendritic cells loaded with tumor antigens. This study is not yet open for participant recruitment. ClinicalTrials.gov Identifier: NCT00610389 Purpose Background: cellular immunotherapy with dendritic cells (DC) loaded with tumor antigens has shown clinical activity, although in a small number of patients. Therefore, it is mandatory to improve the resul...

Data was obtained on the efficacy in a phase I/II study investigating multiple injections of CLL-DCV01 in patients with previously treated B-cell chronic lymphocytic leukemia. This study is fully enrolled (n=9). Efficacy data will be assessed via tumor burden data collected over the next two months. Absolute lymphocyte counts and immunomonitoring data will be compiled by the end of Q1’08.

We obtained data from a trial in small cohorts of patients (3-9) who 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. Our experiences can be summarized as follows: (1) preparation of an autologous dendritic cell based vaccine was feasible for every patient enrolled in our studies; (2) we did not observe vaccination related toxicities beside mild...

Our laboratory has data on autologous dendritic cells loaded with apoptotic leukemic cells from patients with B-CLL used as vaccine in patients. In preclinical experiments DC-loaded with apoptotic leukemic cells were shown to induce a strong preferentially Th1 T-cell response. Apoptotic tumor cells were more effective than lysate, RNA and cell hybrids. A clinical trial has been initiated where autologous dendritic cells are loaded with apoptotic leukemic cells from patients with B-CLL. So far “vaccines” have been produced for six patients. Four patients are...

Our lab obtained first data from a new clinical trial of a DC vaccine administered into irradiated tumours in RCC. Three patients were enrolled and DC vaccine was produced. However only 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.

We have obtained data from monitoring vaccine induced T cell responses for two clinical trials. We found CD8+ and CD4+ T cell responses against the immunological tracers KLH and TK, and against the NTPs and MAGE-3, respectively. Assays used have been 3H-thymidine-incorporation, ELISA, CBA, LDA and 51Cr-release assays. Autologous tumour specific CD8+ and CD4+ T cell clones have also been obtained from the blood and tumour infiltrating lymphocytes. We investigated the role of spontaneous CD4+ T cell responses against the HPV-18 and 16 E6 and E7 proteins in women wi...

We obtained data on anti-tumor responses in melanoma patients that were vaccinated with autologous DCs loaded with a combination of tumor Ag peptides. This study is a collaboration with the lab of Didier Colau and Thierry Boon in Brussels. HLA-DP4/MAGE3 molecules have been prepared to stain ex vivo PBL from immunized melanoma patients.

We have continued recruitment of patients and obtained first data in the two clinical trials of active vaccination in metastatic melanoma. Structural works that have been performed to up-grade the GMP facility for conduction of phase III clinical trials has limited the number of patients recruited. Nonetheless, we were able to complete the vaccination schedule in 4 patients and to perform additional injections in disease free patients, in patients with stable disease or with slowly progressive disease. We could not recruit new patients because the generation in GM...

Data has been obtained from our phase 1 HIV clinical study described here: Study Design: 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 are administered 4 monthly doses of the Arcelis product. Current status: This trial is fully enrolled. Immune response data is encouraging in the first 7 patients for which the analysis has been completed. Six of 7 patients developed CD8+ T-cell immune...

Data have been obtained from a phase 2 study testing PME-CD40L DC in RCC patients with clear cell histology. The Phase 2 trial has the same general design, dosing regimen, endpoints, and immunomonitoring plan as the completed RCC trial. However, the Phase 2 study tests the improved RCC product (i.e., PME-CD40L DC) and is restricted to RCC patients with clear cell histology. As predicted from the in vitro data, the improved PME-CD40L DC product does indeed lead to restoration of both IL-2 and IFN-? responses. Also consistent with our in vitro observation is the...