Journal of Neuro-Oncology

, Volume 99, Issue 2, pp 261–272 | Cite as

Integration of autologous dendritic cell-based immunotherapy in the primary treatment for patients with newly diagnosed glioblastoma multiforme: a pilot study

  • Hilko Ardon
  • Stefaan Van Gool
  • Isabel Spencer Lopes
  • Wim Maes
  • Raf Sciot
  • Guido Wilms
  • Philippe Demaerel
  • Patricia Bijttebier
  • Laurence Claes
  • Jan Goffin
  • Frank Van Calenbergh
  • Steven De Vleeschouwer
Clinical Study - Patient Study

Abstract

Despite resection, radiochemotherapy, and maintenance temozolomide chemotherapy (TMZm), the prognosis of patients with glioblastoma multiforme (GBM) remains poor. We integrated immunotherapy in the primary standard treatment for eight pilot adult patients (median age 50 years) with GBM, to assess clinical and immunological feasibility and toxicity in preparation of a phase I/II protocol HGG-2006. After maximum, safe resection, leukapheresis was performed before radiochemotherapy, and four weekly vaccinations with autologous GBM lysate-loaded monocyte-derived dendritic cells were given after radiochemotherapy. Boost vaccines with lysates were given during TMZm. During the course of vaccination, immunophenotyping showed a relative increase in CD8+CD25+ cells in six of the seven patients, complying with the prerequisites for implementation of immunotherapy in addition to postoperative radiochemotherapy. In five patients, a more than twofold increase in tumor antigen-reacting IFN-γ-producing T cells on Elispot was seen at the fourth vaccination compared with before vaccination. In three of these five patients this more than twofold increase persisted after three cycles of TMZm. Quality of life during vaccination remained excellent. Progression-free survival at six months was 75%. Median overall survival for all patients was 24 months (range: 13–44 months). The only serious adverse event was an ischemic stroke eight months postoperatively. We conclude that tumor vaccination, fully integrated within the standard primary postoperative treatment for patients with newly diagnosed GBM, is feasible and well tolerated. The survival data were used to power a currently running phase I/II trial.

Keywords

Immunotherapy Glioblastoma multiforme Dendritic cell vaccination Brain tumors 

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Hilko Ardon
    • 1
  • Stefaan Van Gool
    • 2
    • 5
  • Isabel Spencer Lopes
    • 2
  • Wim Maes
    • 2
  • Raf Sciot
    • 3
  • Guido Wilms
    • 4
  • Philippe Demaerel
    • 4
  • Patricia Bijttebier
    • 6
  • Laurence Claes
    • 6
  • Jan Goffin
    • 1
  • Frank Van Calenbergh
    • 1
  • Steven De Vleeschouwer
    • 1
  1. 1.Department of Neurosurgery, University Hospital LeuvenCatholic University of LeuvenLeuvenBelgium
  2. 2.Department of Experimental MedicineCatholic University of LeuvenLeuvenBelgium
  3. 3.Department of Pathology, University Hospital LeuvenCatholic University of LeuvenLeuvenBelgium
  4. 4.Department of Imaging, University Hospital LeuvenCatholic University of LeuvenLeuvenBelgium
  5. 5.Department of Child and Woman, University Hospital LeuvenCatholic University of LeuvenLeuvenBelgium
  6. 6.Centre for Clinical Assessment and PsychopathologyCatholic University of LeuvenLeuvenBelgium

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