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Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
06:14

Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus

Published on: May 13, 2021

Histone deacetylase inhibitors augment antitumor efficacy of herpes-based oncolytic viruses

Akihiro Otsuki1, Ankita Patel, Kazue Kasai

  • 1Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, 43210 USA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|July 24, 2008
PubMed

Insights

Histone deacetylase (HDAC) inhibitors enhance the effectiveness of oncolytic herpes simplex virus (HSV) therapy against gliomas. Pretreatment with HDAC inhibitors like valproic acid (VPA) boosts viral replication and antitumor efficacy.

Area of Science:

  • Oncology
  • Virology
  • Pharmacology

Background:

  • Oncolytic herpes simplex virus (HSV) shows promise for treating human malignancies.
  • Histone deacetylase (HDAC) inhibitors are a novel class of antineoplastic agents with known effects on gene expression and cellular responses.
  • Chemotherapeutic adjuvants are needed to improve the efficacy of oncolytic virotherapy.

Purpose of the Study:

  • To investigate the potential of HDAC inhibitors as adjuvants to enhance the antitumor efficacy of oncolytic HSV.
  • To determine if HDAC inhibitors can improve the replication and therapeutic effects of oncolytic HSV in glioma models.

Main Methods:

  • Glioma cells were treated with HDAC inhibitors prior to infection with oncolytic HSV.
  • Viral progeny yield was measured after treatment and infection.
  • Interferon (IFN)-responsive genes and viral gene transcription were analyzed.
  • The efficacy of VPA-pretreated oncolytic HSV was evaluated in a human glioma xenograft model in vivo.

Main Results:

  • Pretreatment with HDAC inhibitors significantly increased the yield of viral progeny in cultured glioma cells.
  • Valproic acid (VPA) was most effective when used as a pretreatment, not concomitantly.
  • VPA pretreatment inhibited IFN-responsive antiviral genes and augmented viral gene transcription.
  • VPA pretreatment improved oncolytic HSV propagation and therapeutic efficacy in vivo.

Conclusions:

  • HDAC inhibitors can serve as effective adjuvants to improve the antitumor efficacy of oncolytic HSV virotherapy.
  • VPA pretreatment enhances oncolytic HSV replication and therapeutic outcomes in glioma models.
  • Targeting epigenetic mechanisms with HDAC inhibitors represents a promising strategy for augmenting oncolytic virotherapy.

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