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p16INK4a als Ziel therapeutischer Impfung

Konzept und Status der klinischen Prüfung bei HPV-assoziierten Kopf-Hals-Tumoren

Targeting p16INK4a by therapeutic vaccination

Concept and status of clinical investigations in HPV-associated head and neck cancers

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Zusammenfassung

Hintergrund

Bis zu 70 % aller Oropharynxkarzinome sind auf Infektionen mit humanen Papillomviren (HPV) zurückzuführen, eine Therapie speziell für Patienten mit HPV-assoziierten Karzinomen gibt es aber bisher nicht. Die Überexpression der viralen Onkogene E6 und E7 führt zu zellulären Veränderungen, die interessante Ansatzpunkte für neue Therapien sind. Eine Folge der E6/E7-Überexpression ist die starke Expression des zellulären Proteins p16INK4a. Die Eliminierung p16INK4a-exprimierender Tumorzellen durch das Immunsystem könnte durch eine therapeutische p16INK4a-Impfung erreicht werden.

Ziel der Arbeit

Der Artikel gibt einen Überblick zu HPV-assoziierten Kopf-Hals-Tumoren und damit verbundener p16INK4a-Expression. Davon ausgehend werden Konzept und Status der klinischen Prüfung der therapeutischen p16INK4a-Impfung beschrieben.

Material und Methoden

Dargestellt wird publizierte Literatur. Des Weiteren ist eine klinische Studie beschrieben. In dieser Phase I/IIa-Studie wurden Patienten mit fortgeschrittenen HPV-assoziierten, p16INK4a-exprimierenden Tumoren mit einem p16INK4a-Peptid geimpft.

Ergebnisse

HPV-assoziierte Kopf-Hals-Tumoren zeigen durchweg eine starke Überexpression des zellulären Proteins p16INK4a. Eine Impfung mit p16INK4a könnte eine neue Therapie für Patienten mit HPV-assoziierten Karzinomen darstellen.

Diskussion

Weitere Studien werden den klinischen Nutzen der therapeutischen p16INK4a-Impfung überprüfen. Kombinationen mit anderen immuntherapeutischen Verfahren sind vor dem Hintergrund einer modulierenden Rolle des Immunsystems vor allem bei HPV-assoziierten Tumoren interessant.

Abstract

Background

Up to 70 % of oropharyngeal cancers are attributable to human papillomavirus (HPV) infection; however, a therapy specific for patients with HPV-associated cancers is currently not available. Overexpression of the viral oncogenes E6 and E7 results in cellular alterations that represent interesting targets for novel therapies. One consequence of E6/E7 overexpression is strong expression of the cellular protein p16INK4a. The elimination of p16INK4a-expressing tumor cells by the immune system could be achieved through a therapeutic p16INK4a vaccine.

Objective

The current article provides an overview of HPV-associated head and neck cancers and the associated p16INK4a expression. Based on this overview, the concept and status of the clinical investigation of therapeutic p16INK4a vaccination is described.

Material and methods

In addition to discussing published literature, a clinical study is described. In this phase I/IIa study, patients with advanced HPV-associated p16INK4a-expressing tumors were vaccinated with a p16INK4a peptide.

Results

HPV-associated head and neck cancers continuously display strong overexpression of the cellular protein p16INK4a. Vaccination with p16INK4a could represent a novel therapy for patients with HPV-associated carcinomas.

Conclusion

Further studies will evaluate the clinical efficacy of therapeutic p16INK4a vaccination. Combinations with other immunotherapeutic approaches are interesting considering the modulating role of the immune system, particularly in HPV-associated tumors.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. M. Reuschenbach gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Originaldaten aus Studien an Menschen oder Tieren. Die im Artikel erwähnte laufende Studie VICORYX „A phase I/IIa study of p16 peptide vaccination combined with Montanide ISA-51 VG in patients with advanced HPV-associated cancers“ wird mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki durchgeführt.

Danksagung

Die Autorin dankt dem gesamten VICORYX-Studienteam, insbesondere M. von Knebel Doeberitz, M. Kloor, E.S. Prigge, F. Faulstich, M. Sauer, K. Urban (Universitätsklinikum Heidelberg), E. Jäger, R. Rafiyan, J. Karbach, C. Pauligk, S. Al Batram (Krankenhaus Nordwest, Frankfurt) und M.W. Dahm, O. Krebs, B. Huber (Fa. Oryx GmbH und Co KG, Baldham).

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  1. Abteilung für Angewandte Tumorbiologie, Institut für Pathologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland

    M. Reuschenbach

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Correspondence to M. Reuschenbach.

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Reuschenbach, M. p16INK4a als Ziel therapeutischer Impfung. HNO 63, 104–110 (2015). https://doi.org/10.1007/s00106-014-2944-z

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  • DOI: https://doi.org/10.1007/s00106-014-2944-z

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