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Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Heather MacTavish1, Jean-Simon Diallo, Baocheng Huang

  • 1Center for Cancer Therapeutics, Ottawa Hospital Research Institute, Ontario, Canada.

Plos One
|February 2, 2011
PubMed

Insights

Histone deacetylase inhibitors (HDI) enhance the effectiveness of oncolytic vaccinia viruses (VV) against cancer. Trichostatin A (TSA) specifically boosted VV replication in resistant cancer cells, improving treatment outcomes.

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Histone deacetylase inhibitors (HDI) modulate innate immune responses, including interferon production.
  • HDIs have previously enhanced the replication of certain viruses like vesicular stomatitis virus and HSV.
  • Tumor-selective oncolytic vaccinia viruses (VV) are under clinical investigation for cancer therapy.

Purpose of the Study:

  • To investigate if HDIs can enhance the efficacy of oncolytic vaccinia viruses (VV) in cancer cell lines resistant to infection.
  • To identify specific HDIs that potentiate VV activity against cancer.

Main Methods:

  • Screening of multiple HDIs for their ability to enhance VV replication and spread.
  • Testing the most effective HDI, Trichostatin A (TSA), in various infection-resistant cancer cell lines.
  • Evaluating the therapeutic effect of TSA and VV combination in preclinical cancer models, including metastasis and xenograft models.

Main Results:

  • Trichostatin A (TSA) significantly enhanced the replication and spread of a tumor-selective vaccinia virus (VV) in multiple infection-resistant cancer cell lines.
  • TSA treatment led to a significant reduction in lung metastases in a B16F10LacZ syngeneic mouse model.
  • The combination of TSA and VV improved survival rates in mice bearing human HCT116 colon tumor xenografts compared to monotherapy.
  • Importantly, TSA did not increase vaccinia virus replication in normal tissues.

Conclusions:

  • Trichostatin A (TSA) selectively enhances the replication and spread of oncolytic vaccinia virus (VV) within cancer cells.
  • The combination of TSA and VV demonstrates therapeutic potential for enhancing oncolytic virotherapy efficacy.
  • This strategy offers a promising approach to overcome cancer cell resistance to viral infection and improve treatment outcomes.

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