Immuntherapie von Hirntumoren

Zusammenfassung

Immuntherapeutische Behandlungsansätze bei Hirntumoren werden schon seit Jahrzehnten als potenziell hilfreich und attraktiv angesehen. Im Gegensatz zum erheblich gestiegenen Verständnis der immunologischen Grundlagen von Tumoren im Gehirn waren die klinischen Fortschritte jedoch lange Zeit vergleichsweise bescheiden. Diese Situation hat sich in den letzten Jahren grundlegend geändert, u. a. durch die Entwicklung neuartiger Vakzinierungskonzepte. Impfstoffe, die aus einem oder mehreren Peptiden bestehen, befinden sich in einem fortgeschrittenen Stadium der klinischen Entwicklung zur Behandlung von Gliomen. Im Rahmen individualisierter Konzepte wird zudem versucht, Vakzinen herzustellen, deren Zusammensetzung auf einer umfangreichen Analyse des Tumorgewebes basiert und somit tumor- bzw. patientenspezifisch ist. Parallel wird derzeit in der Neuroonkologie die Wirksamkeit von Immun-Checkpoint-Inhibitoren untersucht. Diese Medikamente interagieren mit Immunzellrezeptoren, z. B. CTLA-4 oder PD-1, bzw. den dazugehörigen Liganden und sorgen für stärkere und anhaltende Immunantworten, u. a. auch gegen Tumorzellen. Mittlerweile sind immer mehr Daten verfügbar, die nahelegen, dass diese Immuntherapeutika bei Hirnmetastasen wirksam sein können. Unklar ist aber noch, ob auch Patienten mit primären Hirntumoren, z. B. Glioblastomen, von diesem Therapieansatz profitieren. Mehrere Studien untersuchen derzeit den Einsatz von Immun-Checkpoint-Inhibitoren allein oder in Kombination mit Strahlen- bzw. Chemotherapie bei Patienten mit neu diagnostiziertem oder rezidiviertem Glioblastom. Die Ergebnisse der laufenden Studien werden zeigen, ob sich immuntherapeutische Behandlungsansätze in Zukunft als Ergänzung zu den bisher zur Verfügung stehenden Therapieoptionen in der Neuro-Onkologie etablieren können.

Abstract

Immunotherapy has been regarded as a promising therapeutic strategy for brain tumor patients for decades. However, in contrast to the increasing understanding of the immunobiology of brain tumors, only very limited progress has been made in the clinical setting. This situation has now changed with the emergence of novel vaccination concepts. Advanced peptide vaccines comprise peptides from tumor-associated antigens or neoantigens that are exclusively expressed by tumor cells. Vaccines that are generated on an individual basis following large-scale assessments of a patient’s tumor are at an early stage of clinical development and may represent an ideal approach to specifically mount anti-tumor immune responses. Immune checkpoint inhibitors that target CTLA-4 or PD-1 may allow for a powerful activation of the immune system and represent another promising approach. There is an increasing body of evidence that these drugs can exert strong anti-tumor activity against neoplasms in the central nervous system. Therefore, checkpoint inhibitors are currently being investigated in various trials in patients with primary and metastatic brain tumors. Specifically, several trials aim at assessing the activity of antibodies targeting PD-1 or its major ligand, PD-L1, either alone or in combination with conventional treatment such as radiotherapy or alkylating chemotherapy in patients with newly diagnosed or recurrent glioblastoma. The results of the currently ongoing trials will demonstrate whether immunotherapy can be integrated into the standard of care for various brain tumors.

Schlüsselwörter

Hirntumor - Glioblastom - Impfung - CTLA-4 - PD-1

Key words

brain tumor - glioblastoma - vaccination - CTLA-4 - PD-1

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