© Copyright 2009 by the Society for Neuro-Oncology
Received October 23, 2008
Accepted December 24, 2008
Basic and Translational Investigations
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DC vaccination with anti-CD25 treatment leads to long-term immunity against experimental glioma
Wim Maes 1*,
Georgina Galicia Rosas 2,
Bert Verbinnen 2,
Louis Boon 3,
Steven De Vleeschouwer 4,
Jan L. Ceuppens 2,
Stefaan W. Van Gool 5
1 Department of Experimental Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Box 811, Herestraat 49, 3000 Leuven, Belgium
2 Clinical Immunology, Department of Experimental Medicine, Katholieke Universiteit Leuven, University Hospital Gasthuisberg, Leuven, Belgium
3 Bioceros BV, Utrecht, The Netherlands
4 Clinical Immunology, Department of Experimental Medicine, Katholieke Universiteit Leuven, University Hospital Gasthuisberg, Leuven, Belgium; Experimental Neurosurgery and Neuroanatomy, Katholieke Universiteit Leuven, University Hospital Gasthuisberg, Leuven, Belgium
5 Clinical Immunology, Department of Experimental Medicine, Katholieke Universiteit Leuven, University Hospital Gasthuisberg, Leuven, Belgium; Pediatric Hemato-Oncology, Department of Child and Woman, Katholieke Universiteit Leuven, University Hospital Gasthuisberg, Leuven, Belgium
* To whom correspondence should be addressed. E-mail: wim.maes{at}med.kuleuven.be.
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Abstract |
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We studied the feasibility, efficacy, and mechanisms of dendritic cell (DC) immunotherapy against murine malignant glioma in the experimental GL261 intracranial (IC) tumor model. When administered prophylactically, mature DC (DCm), ex vivo loaded with GL261 RNA (DCm-GL261–RNA) protected half of the vaccinated mice against IC glioma, whereas treatment with mock-loaded DCm or DCm loaded with irrelevant antigens did not result in tumor protection. In DCm-GL261–RNA vaccinated mice, a tumor-specific cellular immune response was observed ex vivo in the spleen and tumor-draining lymph node cells. Specificity was also shown in vivo on the level of tumor challenge. Depletion of CD8+ T cells by anti-CD8 treatment at the time of tumor challenge demonstrated their essential role in vaccine-mediated antitumor immunity. Depletion of CD25+ regulatory T cells (Treg) by anti-CD25 treatment (aCD25) strongly enhanced the efficacy of DC vaccination and was on itself also protective, independently of DC vaccination. However, DC vaccination was essential to protect the animals from intracranial tumor re-challenge. No long-term protection was observed in animals that initially received aCD25–treatment only. Both in mice that received DC and/or aCD25 treatment, we retrieved tumor-specific brain-infiltrating cytotoxic T lymphocytes. These data clearly demonstrate the effectiveness of DC vaccination for the induction of long-lasting immunological protection against intracranial glioma. They also show the beneficial effect of Treg depletion in this kind of glioma immunotherapy, even combined with DC vaccination.
Key Words:
anti-CD25, anti-CD8, DC immunotherapy, glioma, regulatory T cells
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