Dendritic cell therapy in glioblastoma multiforme

Abstract

3065 Background: Malignant brain tumors belong to the tumors with unfavorable prognosis. The most aggressive form, glioblastoma multiforme (GBM WHO grade IV glioma), is categorized as incurable with median survivals less than 12–18 months and 90–95% of patients surviving less than 2 years. Here we show that immunotherapy with monocyte-derived dendritic cells (MoDC) can induce a clinical response in advanced GMB, especially when combined with the non human pathogenic oncolytic virus NDV (New Castle Disease Virus). Methods: After isolating monocytes from peripheral blood of n=21 patients dendritic cells were generated ex vivo in the presence of recombinant cytokines (IL-4, GM-CSF) and 2,5% autologous serum. If tumor tissue was available the MoDC were primed on day 5 with tumor- lysate and co-cultured with poly:IC and IFN-alpha. The MoDC were harvested on day 7 of culture and administered to the patients, intradermally. In 5 patients NDV was added to the MoDC for one hour prior to administration. These patients received an infusion with NDV one day before vaccination. Results: We were able to induce a clinical response in 33% (n=7) of the treated patients. The median survival after onset of DC-therapy was 10 months. With respect to primary diagnosis the median survival was 19 months with 1- and 2-years survival rates of 81% and 14%, respectively. Improvement of the clinical response can be observed by combination of NDV. None of the 5 patients treated with this combination therapy died of the disease (9–19 months after primary diagnosis). Three of them (60%) show a response with 2 clear partial remissions (40%). Conclusions: Taken together, a dendritic-cell based therapy can be successful in the treatment of GBM. Enhancement of the therapeutically outcome can be induced by a combination therapy with New Castle Disease Virus leading to the suggestion that there may be an interaction between the dendritic cells and the NDV. No significant financial relationships to disclose.