Onkolytische Virotherapie bei Kopf-Hals-Karzinomen

Zusammenfassung

Ziel Onkolytische Viren (OV) infizieren und töten Krebszellen und lösen eine antitumorale Immunantwort aus. Durch ihr Potenzial, die Immunresistenz von Tumoren zu durchbrechen, könnten OV eine zukünftige zusätzliche Behandlungsoption bei Patient*innen mit fortgeschrittenen Kopf-Hals-Karzinomen (HNC) sein. Wirkungsweise und Modifikationen der OV zur Behandlung von HNC werden erläutert, ebenso die Risiken bei der Anwendung. Ergebnisse präklinischer und klinischer Studien werden vorgestellt.

Methoden Präklinische und klinische Studien zu OV und HNC wurden in der PubMed-Literaturdatenbank und internationalen Studienregistern analysiert. Untersuchungen zum onkolytischen Herpes-Simplex-Virus (HSV), Adenovirus, Vacciniavirus und Reovirus wurden ausgewählt.

Ergebnisse In jüngsten präklinischen Studien wurde eine verstärkte Infektion und Abtötung von Tumorzellen durch OV mit Kapsid- und Genommodifikationen beschrieben. Die meisten klinischen Studien waren Phase-I/II-Studien. In Phase-III-Studien wurden nach Behandlung mit onkolytischem HSV, Adenoviren und Reoviren eine partielle Tumorregression und ein verlängertes Überleben beobachtet. In den meisten Studien wurden OV mit Radiochemotherapie oder Immuntherapie kombiniert.

Schlussfolgerung In den vorliegenden Studien war die OV-Therapie zur Behandlung von Patient*innen mit HNC sicher, oft gut verträglich und zeigte vielversprechende Ergebnisse in Hinsicht auf Ansprechen und Überleben, insbesondere in Kombination mit einer Radiochemotherapie oder Checkpoint-Inhibitoren.

Abstract

Objective Oncolytic viruses (OV) infect and kill cancer cells and elicit an antitumoral immune response. With their potential to break through tumor immunoresistance, OV might be a future combination treatment option in patients with advanced head and neck cancer (HNC). Modes of action, biological modifications, handling and side effects of OV for treatment of HNC are reviewed. Results of preclinical and clinical trials are reported.

Methods Publications and clinical trials dealing with OV and HNC were searched in PubMed and international platforms for clinical study records. Studies on preclinical and clinical trials regarding oncolytic Herpes Simplex Virus (HSV), Adenovirus, Vacciniavirus and Reovirus were selected.

Results Enhanced infection and killing of tumor cells through capsid and genome modifications of OV were reported in recent preclinical studies. Most of the clinical studies were phase-I/II trials. In phase III studies, tumor regression and prolonged survival were observed after treatment with oncolytic HSV, Adenoviruses and Reoviruses. In most trials, OV were combined with chemoradiotherapy or immunotherapy.

Conclusion In the published studies, OV treatment of HNC patients was safe, often well tolerated and showed promising results with regard to response and survival, especially in combination with chemoradiotherapy or checkpoint inhibitors.

Schlüsselwörter

Kopf-Hals-Karzinom - onkolytisches Virus - Tumor-Microenvironment - Immunantwort - genetische Modifikation

Keywords

Head and Neck Cancer - Oncolytic Virus - Tumor Microenvironment - Immune Response - Genetic Engineering

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