Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CCR Focus Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Breast Cancer
      • Clinical Trials
      • Immunotherapy: Facts and Hopes
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Clinical Cancer Research
Clinical Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CCR Focus Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Breast Cancer
      • Clinical Trials
      • Immunotherapy: Facts and Hopes
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Cancer Therapy: Clinical

Cytolytic Virus Activation Therapy for Epstein-Barr Virus–Driven Tumors

Maarten A. Wildeman, Zlata Novalić, Sandra A.W.M. Verkuijlen, Hedy Juwana, Alwin D.R. Huitema, I. Bing Tan, Jaap M. Middeldorp, Jan Paul de Boer and Astrid E. Greijer
Maarten A. Wildeman
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zlata Novalić
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra A.W.M. Verkuijlen
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hedy Juwana
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alwin D.R. Huitema
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
I. Bing Tan
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaap M. Middeldorp
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jan Paul de Boer
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Astrid E. Greijer
Authors' Affiliations: Departments of 1Head and Neck Oncology and Surgery and 2Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital; 3Department of Pathology, VU University Medical Center; and 4Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1078-0432.CCR-12-0574 Published September 2012
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Purpose: Nasopharyngeal carcinoma (NPC) is causally linked to Epstein–Barr virus (EBV) infection. Because all tumor cells carry EBV, the virus itself is a potential target for therapy. In these tumor cells, EBV hides in a latent state and expresses only a few non-immunogenic proteins for EBV maintenance and contributes to tumor growth. We developed a cytolytic virus activation (CLVA) therapy for NPC treatment, reactivating latent EBV, triggering immune recognition, and inducing susceptibility to antiviral therapy.

Experimental Design: CLVA therapy combines gemcitabine (GCb) and valproic acid (VPA) for virus activation and tumor clearance with (val)ganciclovir (GCV) as the antiviral drug to block virus replication and kill proliferating virus-infected cells. CLVA treatment was optimized and validated in NPC cell lines and subsequently tested in 3 Dutch patients with NPC that was refractory to conventional treatment.

Results: In NPC cell lines, both GCb and VPA can induce the lytic cycle of EBV. Their combination resulted in a strong synergistic effect. The addition of GCV resulted in higher cytotoxicity compared with chemotherapy alone, which was not observed in EBV-negative cells. CLVA therapy was analyzed in 3 patients with end-stage NPC. Patients developed increased levels of viral DNA in the circulation originating from apoptotic tumor cells, had disease stabilization, and experienced improved quality of life.

Conclusions: Our results in the initial CLVA-treated patients indicate that the therapy had a biological effect and was well tolerated with only moderate transient toxicity. This new virus-specific therapy could open a generic approach for treatment of multiple EBV-associated malignancies. Clin Cancer Res; 18(18); 5061–70. ©2012 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Received February 21, 2012.
  • Revision received June 19, 2012.
  • Accepted June 20, 2012.
  • ©2012 American Association for Cancer Research.
View Full Text
PreviousNext
Back to top
Clinical Cancer Research: 18 (18)
September 2012
Volume 18, Issue 18
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Clinical Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Cytolytic Virus Activation Therapy for Epstein-Barr Virus–Driven Tumors
(Your Name) has forwarded a page to you from Clinical Cancer Research
(Your Name) thought you would be interested in this article in Clinical Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Cytolytic Virus Activation Therapy for Epstein-Barr Virus–Driven Tumors
Maarten A. Wildeman, Zlata Novalić, Sandra A.W.M. Verkuijlen, Hedy Juwana, Alwin D.R. Huitema, I. Bing Tan, Jaap M. Middeldorp, Jan Paul de Boer and Astrid E. Greijer
Clin Cancer Res September 15 2012 (18) (18) 5061-5070; DOI: 10.1158/1078-0432.CCR-12-0574

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Cytolytic Virus Activation Therapy for Epstein-Barr Virus–Driven Tumors
Maarten A. Wildeman, Zlata Novalić, Sandra A.W.M. Verkuijlen, Hedy Juwana, Alwin D.R. Huitema, I. Bing Tan, Jaap M. Middeldorp, Jan Paul de Boer and Astrid E. Greijer
Clin Cancer Res September 15 2012 (18) (18) 5061-5070; DOI: 10.1158/1078-0432.CCR-12-0574
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Grant Support
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Biomarker Analysis from the BERIL-1 Study
  • Radiation and TGFβ Blockade in Metastatic Breast Cancer
  • Opioids in Clinical Samples Modulate TLR4
Show more Cancer Therapy: Clinical
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • CCR Focus Archive
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Clinical Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Clinical Cancer Research
eISSN: 1557-3265
ISSN: 1078-0432

Advertisement