Laryngorhinootologie 2022; 101(10): 787-796
DOI: 10.1055/a-1901-9214
Übersicht

Onkolytische Virotherapie bei Kopf-Hals-Karzinomen

Oncolytic virotherapy in head and neck cancer
1   Universitätsklinik für Hals-, Nasen- und Ohrenheilkunde, Medizinische Universität Innsbruck, Innsbruck, Austria (Ringgold ID: RIN155820)
,
Monika Petersson
2   ViraTherapeutics GmbH, Rum, Austria
,
Herbert Riechelmann
1   Universitätsklinik für Hals-, Nasen- und Ohrenheilkunde, Medizinische Universität Innsbruck, Innsbruck, Austria (Ringgold ID: RIN155820)
› Author Affiliations

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.



Publication History

Received: 07 June 2021

Accepted after revision: 30 June 2022

Article published online:
17 August 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Sung H, Ferlay J, Siegel RL. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians 2021; 71: 209-249
  • 2 Johnson DE, Burtness B, Leemans CR. et al. Head and neck squamous cell carcinoma. Nature reviews Disease primers 2020; 6: 92
  • 3 Dejaco D, Riedl D, Gasser S. et al. A Tool for Rapid Assessment of Functional Outcomes in Patients with Head and Neck Cancer. Cancers 2021; 13
  • 4 Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: Recent advances and future directions. Oral oncology 2019; 99: 104460
  • 5 Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer science 2016; 107: 1373-1379
  • 6 Schoggins JW. Interferon-Stimulated Genes: What Do They All Do?. Annual review of virology 2019; 6: 567-584
  • 7 Achard C, Surendran A, Wedge ME. et al. Lighting a Fire in the Tumor Microenvironment Using Oncolytic Immunotherapy. EBioMedicine 2018; 31: 17-24
  • 8 Jayawardena N, Burga LN, Poirier JT. et al. Virus-Receptor Interactions: Structural Insights For Oncolytic Virus Development. Oncolytic virotherapy 2019; 8: 39-56
  • 9 Hill C, Carlisle R. Achieving systemic delivery of oncolytic viruses. Expert Opinion on Drug Delivery 2019; 16: 607-620
  • 10 Harrington K, Freeman DJ, Kelly B. et al. Optimizing oncolytic virotherapy in cancer treatment. Nat Rev Drug Discov 2019; 18: 689-706
  • 11 de Graaf JF, de Vor L, Fouchier RAM. et al. Armed oncolytic viruses: A kick-start for anti-tumor immunity. Cytokine & growth factor reviews 2018; 41: 28-39
  • 12 Chesney J, Puzanov I, Collichio F. et al. Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018; 36: 1658-1667
  • 13 Harrington KJ, Michielin O, Malvehy J. et al. A practical guide to the handling and administration of talimogene laherparepvec in Europe. OncoTargets and therapy 2017; 10: 3867-3880
  • 14 Harrington KJ, Hingorani M, Tanay MA. et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clinical cancer research: an official journal of the American Association for Cancer Research 2010; 16: 4005-4015
  • 15 Harrington KJ, Kong A, Mach N. et al. Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Clinical cancer research : an official journal of the American Association for Cancer Research 2020; 26: 5153-5161
  • 16 Ganly I, Kirn D, Eckhardt G. et al. A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res 2000; 6: 798-806
  • 17 Mell LK, Brumund KT, Daniels GA. et al. Phase I Trial of Intravenous Oncolytic Vaccinia Virus (GL-ONC1) with Cisplatin and Radiotherapy in Patients with Locoregionally Advanced Head and Neck Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 2017; 23: 5696-5702
  • 18 Karapanagiotou EM, Roulstone V, Twigger K. et al. Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research 2012; 18: 2080-2089
  • 19 Oncolytics Biotech Inc. Oncolytics Biotech Inc. Provides Update on Phase III Study of REOLYSIN in Head and Neck Cancers. In: September 12, 2012.
  • 20 Hu-Lieskovan S, Ribas A. New Combination Strategies Using Programmed Cell Death 1/Programmed Cell Death Ligand 1 Checkpoint Inhibitors as a Backbone. Cancer journal (Sudbury, Mass) 2017; 23: 10-22
  • 21 Heise C, Hermiston T, Johnson L. et al. An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med 2000; 6: 1134-1139
  • 22 Smith GL, Benfield CTO, Maluquer de Motes C. et al. Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity. J Gen Virol 2013; 94: 2367-2392
  • 23 Kolk A, Jubitz N, Mengele K. et al. Expression of Y-box-binding protein YB-1 allows stratification into long- and short-term survivors of head and neck cancer patients. Br J Cancer 2011; 105: 1864-1873
  • 24 Chang J, Zhao X, Wu X. et al. A Phase I study of KH901, a conditionally replicating granulocyte-macrophage colony-stimulating factor: armed oncolytic adenovirus for the treatment of head and neck cancers. Cancer biology & therapy 2009; 8: 676-682
  • 25 Tolonen N, Doglio L, Schleich S. et al. Vaccinia virus DNA replication occurs in endoplasmic reticulum-enclosed cytoplasmic mini-nuclei. Mol Biol Cell 2001; 12: 2031-2046
  • 26 Shmulevitz M, Pan LZ, Garant K. et al. Oncogenic Ras promotes reovirus spread by suppressing IFN-beta production through negative regulation of RIG-I signaling. Cancer Res 2010; 70: 4912-4921
  • 27 Wang H, Li ZY, Liu Y. et al. Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat Med 2011; 17: 96-104
  • 28 Kesselring R, Thiel A, Pries R. et al. The complement receptors CD46, CD55 and CD59 are regulated by the tumour microenvironment of head and neck cancer to facilitate escape of complement attack. Eur J Cancer 2014; 50: 2152-2161
  • 29 Rosewell Shaw A, Porter CE, Watanabe N. et al. Adenovirotherapy Delivering Cytokine and Checkpoint Inhibitor Augments CAR T Cells against Metastatic Head and Neck Cancer. Mol Ther 2017; 25: 2440-2451
  • 30 Hill C, Carlisle R. Achieving systemic delivery of oncolytic viruses. Expert Opin Drug Deliv 2019; 16: 607-620
  • 31 Jaime-Ramirez AC, Yu JG, Caserta E. et al. Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma. Mol Ther Oncolytics 2017; 5: 87-96
  • 32 Ilett EJ. Delivery of Oncolytic Reovirus by Cell Carriers. Methods Mol Biol 2020; 2058: 229-236
  • 33 Michielin O, van Akkooi ACJ, Ascierto PA. et al. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2019; 30: 1884-1901
  • 34 Xia ZJ, Chang JH, Zhang L. et al. Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus. Ai Zheng 2004; 23: 1666-1670
  • 35 Heo J, Reid T, Ruo L. et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med 2013; 19: 329-336
  • 36 Lauer UM, Schell M, Beil J. et al. Phase I Study of Oncolytic Vaccinia Virus GL-ONC1 in Patients with Peritoneal Carcinomatosis. Clin Cancer Res 2018; 24: 4388-4398
  • 37 Choi IK, Yun CO. Recent developments in oncolytic adenovirus-based immunotherapeutic agents for use against metastatic cancers. Cancer Gene Ther 2013; 20: 70-76
  • 38 Greenhalgh T. How to read a paper. Getting your bearings (deciding what the paper is about). BMJ (Clinical research ed) 1997; 315: 243-246
  • 39 Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247
  • 40 Fang L, Cheng Q, Zhao J. et al. A p53-independent apoptotic mechanism of adenoviral mutant E1A was involved in its selective antitumor activity for human cancer. Oncotarget 2016; 7: 48309-48320
  • 41 Cooper T, Biron VL, Fast D. et al. Oncolytic activity of reovirus in HPV positive and negative head and neck squamous cell carcinoma. J Otolaryngol Head Neck Surg 2015; 44: 8
  • 42 Mace AT, Ganly I, Soutar DS. et al. Potential for efficacy of the oncolytic Herpes simplex virus 1716 in patients with oral squamous cell carcinoma. Head & neck 2008; 30: 1045-1051
  • 43 Rodriguez-Garcia A, Gimenez-Alejandre M, Rojas JJ. et al. Safety and efficacy of VCN-01, an oncolytic adenovirus combining fiber HSG-binding domain replacement with RGD and hyaluronidase expression. Clinical cancer research: an official journal of the American Association for Cancer Research 2015; 21: 1406-1418
  • 44 Bishnoi S, Tiwari R, Gupta S. et al. Oncotargeting by Vesicular Stomatitis Virus (VSV): Advances in Cancer Therapy. Viruses 2018; 10
  • 45 Schüttrumpf L, Marschner S, Scheu K. et al. Definitive chemoradiotherapy in patients with squamous cell cancers of the head and neck – results from an unselected cohort of the clinical cooperation group “Personalized Radiotherapy in Head and Neck Cancer”. Radiation oncology 2020; 15 (01) 7
  • 46 Fares CM, Allen EMV, Drake CG. et al. Mechanisms of Resistance to Immune Checkpoint Blockade: Why Does Checkpoint Inhibitor Immunotherapy Not Work for All Patients?. American Society of Clinical Oncology Educational Book 2019; 147-164
  • 47 Fakih M, Wang D, Harb W. et al. SPICE, a phase I study of enadenotucirev in combination with nivolumab in tumours of epithelial origin: Analysis of the metastatic colorectal cancer patients in the dose escalation phase. Annals of Oncology 2019; 30: v231
  • 48 Mehra R, Seiwert TY, Gupta S. et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. British journal of cancer 2018; 119: 153-159