Treatment with demethylating agent, 5-aza-2′-deoxycytidine enhances therapeutic HPV DNA vaccine potency

Dan Lu, Talia Hoory, Archana Monie, Annie Wu, Mei Cheng Wang, Chien Fu Hung

Research output: Contribution to journalArticlepeer-review

Abstract

DNA vaccines have emerged as a potential alternative to current strategies to control cancer for their safety, stability and ease of preparation. We have previously demonstrated that a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) can generate significant E7-specific immune responses and antitumor effects in vaccinated mice, thus enhancing DNA vaccine potency. Another strategy to improve DNA vaccine potency is by enhancing the level of expression of the antigen encoded in the vaccine. DNA methylation has been shown to lead to silencing of the genes that would affect the expression of the encoded antigen of the DNA vaccines. In the current study, we reasoned that CRT/E7 DNA vaccination combined with demethylating agent, 5-aza-2′-deoxycytidine (DAC) would lead to upregulation of CRT/E7 expression, resulting in improved DNA vaccine potency. We found that pre-treatment with DAC led to increased CRT/E7 DNA expression, leading to enhanced E7-specific CD8+ T cell immune responses as well as the antitumor effects generated by the CRT/E7 DNA vaccine. Thus, our data suggest that combination of CRT/E7 DNA vaccination with DAC treatment may represent a potentially promising approach to control HPV-associated malignancies. The clinical implications of this study are discussed.

Original languageEnglish (US)
Pages (from-to)4363-4369
Number of pages7
JournalVaccine
Volume27
Issue number32
DOIs
StatePublished - Jul 9 2009

Keywords

  • 5-Aza-2′-deoxycytidine (DAC)
  • Calreticulin (CRT)
  • DNA vaccine
  • HPV-16 E7

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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