Immunological analysis of phase II glioblastoma dendritic cell vaccine (Audencel) trial: immune system characteristics influence outcome and Audencel up-regulates Th1-related immunovariables

Friedrich Erhart, Johanna Buchroithner, René Reitermaier, Katrin Fischhuber, Simone Klingenbrunner, Ido Sloma, Dror Hibsh, Renana Kozol, Sol Efroni, Gerda Ricken, Adelheid Wöhrer, Christine Haberler, Johannes Hainfellner, Günther Krumpl, Thomas Felzmann, Alexander M. Dohnal, Christine Marosi, Carmen Visus

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36 Scopus citations


Audencel is a dendritic cell (DC)-based cellular cancer immunotherapy against glioblastoma multiforme (GBM). It is characterized by loading of DCs with autologous whole tumor lysate and in vitro maturation via "danger signals". The recent phase II "GBM-Vax" trial showed no clinical efficacy for Audencel as assessed with progression-free and overall survival in all patients. Here we present immunological research accompanying the trial with a focus on immune system factors related to outcome and Audencel's effect on the immune system. Methodologically, peripheral blood samples (from apheresis before Audencel or venipuncture during Audencel) were subjected to functional characterization via enzyme-linked immunospot (ELISPOT) assays connected with cytokine bead assays (CBAs) as well as phenotypical characterization via flow cytometry and mRNA quantification. GBM tissue samples (from surgery) were subjected to T cell receptor sequencing and immunohistochemistry. As results we found: Patients with favorable pre-existing anti-tumor characteristics lived longer under Audencel than Audencel patients without them. Pre-vaccination blood CD8+ T cell count and ELISPOT Granzyme B production capacity in vitro upon tumor antigen exposure were significantly correlated with overall survival. Despite Audencel's general failure to induce a significant clinical response, it nevertheless seemed to have an effect on the immune system. For instance, Audencel led to a significant up-regulation of the Th1-related immunovariables ELISPOT IFNγ, the transcription factor T-bet in the blood and ELISPOT IL-2 in a dose-dependent manner upon vaccination. Post-vaccination levels of ELISPOT IFNγ and CD8+ cells in the blood were indicative of a significantly better survival. In summary, Audencel failed to reach an improvement of survival in the recent phase II clinical trial. No clinical efficacy was registered. Our concomitant immunological work presented here indicates that outcome under Audencel was influenced by the state of the immune system. On the other hand, Audencel also seemed to have stimulated the immune system. Overall, these immunological considerations suggest that DC immunotherapy against glioblastoma should be studied further - with the goal of translating an apparent immunological response into a clinical response. Future research should concentrate on investigating augmentation of immune reactions through combination therapies or on developing meaningful biomarkers.

Original languageEnglish
Pages (from-to)135
Number of pages1
JournalActa neuropathologica communications
Issue number1
StatePublished - 5 Dec 2018

Bibliographical note

Funding Information:
This work was supported by the Austrian Research Promotion Agency (“Probio 1 + 2”, 837897/848202), the European Program IAPP-24 (“Modicell”, 285875), and the Society for Austrian NeuroOncology (SANO).


  • Cancer immunotherapy
  • Dendritic cell
  • Glioblastoma multiforme
  • Immunology


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