IL-2 Gentherapie bei HNO-Karzinomen

Zusammenfassung

Patienten mit Plattenepithelkarzinomen des Kopf-Hals-Bereiches weisen eine supprimierte antitumorale Immunantwort auf. Eine Möglichkeit zur Immunrestauration besteht in der lokalen, d. h. intratumoralen, oder systemischen Gabe von positiv-regulatorischen Zytokinen wie z. B. Interleukin-2 (IL-2). IL-2 nimmt eine zentrale Stellung in der Aktivierung der zellvermittelten Immunantwort ein. In einer Vielzahl von Studien konnte der antitumorale Effekt dieses Zytokins belegt werden. Nachteilig sind jedoch die kurze Halbwertszeit, die die Erzielung antitumoral wirksamer Gewebespiegel bei lokaler Applikation einschränkt, und die bei systemischer Gabe oftmals stark toxischen Nebenwirkungen. In Verbindung mit den Fortschritten in der Molekularbiologie war dies Anlass zur Entwicklung gentherapeutischer Strategien, da die lokale Expression von IL-2 hilft, die systemische Toxizität zu vermeiden bei gleichzeitig prolongierter Wirkung im Vergleich zur einmaligen Zytokin-, i. e. Protein-Gabe.

Die vorliegende Arbeit gibt einen Überblick über die Strategien, die auf der Applikation von IL-2 Zytokin, i. e. Protein, und der IL-2 Gentherapie beruhen unter besonderer Berücksichtigung dieser Behandlungsform bei Karzinomen im Kopf-Hals-Bereich. Zusammen mit den Resultaten bereits publizierter Studien ist nach unserer Meinung die Anwendung einer IL-2 Gentherapie am Patienten - wie sie bereits in Form einer Phase I-Studie in unserer Klinik durchgeführt wird - lohnenswert.

Targeting Head and Neck Cancer by IL-2-Mediated Gene Therapy: From Bench to Bedside - A Review

Suppressed cellular immunity is common in patients with squamous cell carcinoma of the head and neck (HNSCC). It was demonstrated in previous studies that administration of interleukin 2 (IL-2) results in enhanced antitumoral immunity in vitro as well as in vivo. Since the serum half-life of IL-2 is relatively short, repeated applications are necessary to achieve therapeutically effective serum concentrations, but this strategy might cause severe side effects. Therefore, methods that provide high local cytokine levels over a prolonged period of time without the need for repeated injections are desirable. Gene therapy as an innovative treatment approach using tumor cells stably transduced to produce IL-2 might meet these criteria. In vitro manipulated tumor cells, if readministered in the vicinity of non-manipulated tumor cells, may enhance a specific anti-tumor response in vivo without systemic side effects.

The present manuscript reviews the current literature dealing with IL-2-protein and -gene therapy with special emphasis on head and neck cancer. Our own in vitro results with IL-2 gene therapy in conjunction with published data from other authors argue in favour of an in vivo approach for this therapeutic strategy that is currently in progress in our department.

Schlüsselwörter:

Plattenepithelkarzinome des Kopf-Hals-Bereiches - Gentherapie - Interleukin 2 - IL-2

Key words:

Squamous cell carcinoma of the head and neck - Gene therapy - Interleukin 2 - IL-2

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