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Concepts in glioma immunotherapy

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Immunotherapeutic concepts in neurooncology have been developed for many decades but have mainly been hampered by poor definition of relevant antigens and selective measures to target the central nervous system. Independent of the recent remarkable successes in clinical immunooncology with checkpoint inhibitors and vaccines, immunotherapy of brain tumors in general and gliomas in particular has evolved with novel neurooncology-specific concepts over the past years providing new phase 1 approaches of individualized immunotherapy to first phase three clinical trials. These concepts are driven by a high medical need in the absence of approved targeted therapies and refute the classic dogma that the central nervous system is immune-privileged and hence inaccessible to potent antitumor immunity. Instead, measures have been taken to improve the odds for successful immunotherapies, including rational targeting of relevant antigens and integration of immunotherapies into standard of care primary radiochemotherapy to increase the efficacy of antitumor immunity in a meaningful time window. This review highlights concepts and challenges associated with epitope discovery and selection and trial design.

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Abbreviations

APC:

Antigen-presenting cell

BBB:

Blood–brain barrier

CAR:

Chimeric antigen receptor

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

DC:

Dendritic cell

EGF:

Epidermal growth factor

EGFRvIII:

Epidermal growth factor receptor variant III

GAPVAC:

Glioma Actively Personalized Vaccine Consortium

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

gp100:

Glycoprotein 100

HLA:

Human leukocyte antigen

IDH1:

Isocitrate dehydrogenase type 1

JCV:

John Cunningham virus

KLH:

Keyhole limpet hemocyanin

MAGE:

Melanoma-associated antigen

MGMT:

O-6-methylguanine-DNA methyltransferase

MHC:

Major histocompatibility complex

OS:

Overall survival

PD-1:

Programmed cell death 1

PD-L1:

PD ligand 1

SOX:

SRY-box

TAA:

Tumor-associated antigen

TRP-2:

Tyrosinase-related protein 2

TSA:

Tumor-specific antigen

WES:

Whole-exome sequencing

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Authors and Affiliations

  1. DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Michael Platten, Lukas Bunse & Theresa Bunse

  2. Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Michael Platten & Wolfgang Wick

  3. National Center of Tumor Diseases (NCT), University Hospital, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany

    Michael Platten & Wolfgang Wick

  4. DKTK Clinical Cooperation Unit Neurooncology, German Cancer Research Center [DKFZ], Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Wolfgang Wick

Authors
  1. Michael Platten
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  2. Lukas Bunse
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  3. Wolfgang Wick
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  4. Theresa Bunse
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Corresponding author

Correspondence to Michael Platten.

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Conflicts of interest

Michael Platten, Wolfgang Wick and Theresa Bunse are inventors on a patent application entitled “Means and methods for treating or diagnosing IDH1 R132H mutant-positive cancers” (WO 2013/102641 A1, PCT/EP2013/050048). Michael Platten, Lukas Bunse and Theresa Bunse are inventors on a patent application entitled “Method for the Detection of Antigen Presentation” (WO 2016/066524, PCT/EP2015/074506).

Additional information

This paper is a Focussed Research Review based on a presentation given at the Thirteenth Annual Meeting of the Association for Cancer Immunotherapy (CIMT), held in Mainz, Germany, 11th–13th May, 2015. It is part of a series of Focussed Research Reviews and meeting report in Cancer Immunology, Immunotherapy.

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Platten, M., Bunse, L., Wick, W. et al. Concepts in glioma immunotherapy. Cancer Immunol Immunother 65, 1269–1275 (2016). https://doi.org/10.1007/s00262-016-1874-x

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  • DOI: https://doi.org/10.1007/s00262-016-1874-x

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