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Nat Rev Neurol. 2017 Jun;13(6):363-374. doi: 10.1038/nrneurol.2017.64. Epub 2017 May 12.

Vaccine-based immunotherapeutic approaches to gliomas and beyond.

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Department of Neurology and Brain Tumour Centre, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
Department of Medicine I and Comprehensive Cancer Centre CNS Unit, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Neurology Clinic, Heidelberg University Medical Centre and Neuro-oncology Programme, National Centre for Tumour Diseases Heidelberg, Im Neuenheimer Feld (INF) 400, 69120 Heidelberg, Germany.
Dana-Farber Cancer Institute, 450 Brookline Avenue, D-2134, Boston 02215-5450, Massachusetts, USA.
Neurology Clinic, Mannheim Medical Centre, Heidelberg University and Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumour Immunology, German Cancer Research Centre, Im Neuenheimer Feld (INF) 280, 69120 Heidelberg, Germany.
Department of Neurosurgery, Duke University Medical Center, 200 Trent Drive, Duke South, Blue Zone, 1st Floor, Room 1554, Durham 27710, North Carolina, USA.


Astrocytic and oligodendroglial gliomas are intrinsic brain tumours characterized by infiltrative growth and resistance to classic cancer therapies, which renders them inevitably lethal. Glioblastoma, the most common type of glioma, also exhibits neoangiogenesis and profound immunosuppressive properties. Accordingly, strategies to revert glioma-associated immunosuppression and promote tumour-directed immune responses have been extensively explored in rodent models and in large clinical trials of tumour immunotherapy. This Review describes vaccination approaches investigated for the treatment of glioma. Several strategies have reached phase III clinical trials, including vaccines targeting epidermal growth factor receptor variant III, and the use of either immunogenic peptides or tumour lysates to stimulate autologous dendritic cells. Other approaches in early phases of clinical development employ multipeptide vaccines such as IMA-950, cytomegalovirus-derived peptides, or tumour-derived peptides such as heat shock protein-96 peptide complexes and the Arg132His mutant form of isocitrate dehydrogenase. However, some preclinical trial data suggest that addition of immunomodulatory reagents such as immune checkpoint inhibitors, transforming growth factor-β inhibitors, signal transducer and activator of transcription 3 inhibitors, or modifiers of tryptophan metabolism could augment the therapeutic activity of vaccination and overcome glioma-associated immunosuppression.


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