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

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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.

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Acknowledgments

We thank Katja Vandenbrande and Goedele Stegen for their excellent technical assistance. We thank the department of hematology for the care provided at time of the leukapheresis. We thank the clinic for radiotherapy for irradiating the tumor lysate preparations. This project is supported by the Olivia Hendrickx Research Fund (www.olivia.be), the Herman Memorial Research Fund (www.hmrf.be), the TBM program of the IWT—Flanders (www.iwt.be), the Belgian Foundation Against Cancer (www.cancer.be), and private initiatives. HSA was provided by the Belgian Red Cross and Baxter. Steven De Vleeschouwer is supported by the “Klinisch onderzoeksfonds” from the University Hospital Leuven. Stefaan Van Gool is Senior Clinical Investigator of the Fund for Scientific Research—Flanders (Belgium) (F.W.O.-Vlaanderen).

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Authors and Affiliations

  1. Department of Neurosurgery, University Hospital Leuven, Catholic University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Hilko Ardon, Jan Goffin, Frank Van Calenbergh & Steven De Vleeschouwer

  2. Department of Experimental Medicine, Catholic University of Leuven, Leuven, Belgium

    Stefaan Van Gool, Isabel Spencer Lopes & Wim Maes

  3. Department of Pathology, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium

    Raf Sciot

  4. Department of Imaging, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium

    Guido Wilms & Philippe Demaerel

  5. Department of Child and Woman, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium

    Stefaan Van Gool

  6. Centre for Clinical Assessment and Psychopathology, Catholic University of Leuven, Leuven, Belgium

    Patricia Bijttebier & Laurence Claes

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  1. Hilko Ardon
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  2. Stefaan Van Gool
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Correspondence to Hilko Ardon.

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Ardon, H., Van Gool, S., Lopes, I.S. et al. Integration of autologous dendritic cell-based immunotherapy in the primary treatment for patients with newly diagnosed glioblastoma multiforme: a pilot study. J Neurooncol 99, 261–272 (2010). https://doi.org/10.1007/s11060-010-0131-y

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