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Immuntherapien bei Gliomen

Glioma immunotherapy

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Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Immuntherapeutische Behandlungsansätze für Gliome mit dem Ziel, einerseits gegen den Tumor gerichtete Immunantworten zu stärken und andererseits dem immunsuppressiven Tumormikromilieu entgegenzuwirken, werden seit Jahrzehnten in präklinischen und klinischen Studien untersucht, ohne dass es bisher eine zugelassene Immuntherapie für die Behandlung von primären Hirntumoren gibt. Dennoch erfährt die Neuroonkoimmunologie aktuell sowohl aufgrund neuer diagnostischer Möglichkeiten und zielgerichteter Therapieoptionen als auch aufgrund erfolgsversprechender Ergebnisse bei systemischen Tumoren ein gesteigertes Interesse.

Ziel

Dieser Artikel gibt einen Überblick über aktuelle Konzepte zur Immuntherapie bei Gliomen und fasst bisherige Studienergebnisse zusammen.

Ergebnisse

Während erste klinische Erfahrungen zum Einsatz von Immuncheckpointinhibitoren bei Gliomen keine grundlegenden Sicherheitsbedenken ergaben, scheint auf Grundlage der bisherigen Studienergebnisse die Wirksamkeit zumindest einer Monotherapie in nicht selektierten Patientenpopulationen bei malignen Gliomen begrenzt zu sein. Klinische Ergebnisse zu Kombinationsbehandlungen, beispielsweise mit T‑Zell-basierten Therapieansätzen wie antigenspezifischen Vakzinierungen, stehen aus. Diese nutzen meist Peptidimpfstoffe, die gegen Tumorantigene gerichtet sind, um eine möglichst effektive und gleichzeitig spezifische Antitumorimmunantwort zu generieren. Neben Impfstoffen gegen individuell variable Antigene eignen sich insbesondere rekurrente Neoepitope wie eine in Glioblastomen vorkommenden Splicevariante des epidermalen Wachstumsfaktors (EGFRvIII) oder eine in diffusen Gliomen vorkommende Punktmutation im Gen der Isocitratdehydrogenase-1 (IDH1R132H) als Vakzinierungsziel.

Abstract

Background

Immunotherapeutic approaches for treatment of malignant gliomas aim at inducing effective anti-tumor immune responses while counteracting the immunosuppressive tumor microenvironment. Despite extensive preclinical and clinical research during the last decades, there are currently no approved immunotherapeutic drugs for primary brain tumors; however, neuro-oncoimmunology is currently experiencing major interest due to new diagnostic and targeted therapy options as well as due to promising results in systemic tumors.

Objective

This article provides an overview of current concepts for glioma immunotherapy and summarizes the results of available clinical trials.

Results

While first clinical experiences with the administration of immune checkpoint inhibitors for gliomas did not raise any safety concerns, the efficacy of immune checkpoint monotherapy for malignant gliomas appears to be limited in an unselected patient population. Clinical results on combination treatment, such as T cell-based therapy approaches with antigen-specific vaccinations are pending. This involves mostly peptide vaccines that are directed against tumor antigens in order to generate an effective and at the same time specific anti-tumor immune response. In addition to vaccines against individually variable antigens, recurrent neoepitopes are particularly suitable as a target of vaccination, such as a splice variant of the epidermal growth factor (EGFRvIII) occurring in glioblastomas and a point mutation occurring in diffuse gliomas in the gene of isocitrate dehydrogenase-1 (IDH1R132H).

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Authors and Affiliations

  1. Neurologische Universitätsklinik Heidelberg und Nationales Zentrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland

    Katharina Ochs,  Lukas Bunse,  Wolfgang Wick &  Michael Platten

  2. Klinische Kooperationseinheit Neuroimmunologie und Hirntumorimmunologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Deutschland

    Katharina Ochs,  Lukas Bunse, Iris Mildenberger &  Michael Platten

  3. Neurologische Universitätsklinik Mannheim, Universitätsmedizin Mannheim, Universität Heidelberg, Theodor-Kutzer-Ufer 1–3, 68167, Mannheim, Deutschland

    Iris Mildenberger &  Michael Platten

Authors
  1. Katharina Ochs
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  2. Lukas Bunse
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  3. Iris Mildenberger
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  4. Wolfgang Wick
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  5. Michael Platten
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Corresponding authors

Correspondence to Katharina Ochs or Michael Platten.

Ethics declarations

Interessenkonflikt

L. Bunse, W. Wick und M. Platten sind Inhaber zweier Patente zur IDH1-Vakzinierung. K. Ochs und I. Mildenberger geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Ochs, K., Bunse, L., Mildenberger, I. et al. Immuntherapien bei Gliomen. Onkologe 23, 831–837 (2017). https://doi.org/10.1007/s00761-017-0258-y

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  • DOI: https://doi.org/10.1007/s00761-017-0258-y

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