Potential role for epigenetic modulatory drugs in the enhancement of cancer/germ-line antigen vaccine efficacy

Research output: Contribution to journalReview article

72 Citations (Scopus)

Abstract

The discovery of epigenetic silencing as a key mechanism of tumor suppressor gene inactivation in human cancer has led to great interest in utilizing epigenetic modulatory drugs as cancer therapeutics. It is less appreciated that medically important tumor-associated antigens, particularly the Cancer Testis or Cancer/Germ-line family of antigens (CG antigens), which are being actively tested as cancer vaccine targets, are epigenetically activated in many human cancers. However, a major limitation to the therapeutic value of CG antigen-directed vaccines is the limited and heterogeneous expression of CG antigens in tumors. Recent work has begun to dissect the specific epigenetic mechanisms controlling differential expression of CG antigen genes in human cancers. From a clinical perspective, convincing data indicate that epigenetic modulatory agents, including DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, robustly promote the expression of CG antigens, as well as class I major histocompatibility complex (MHC I) and other immune costimulatory molecules, in tumors. Importantly, the effects of these agents on CG antigen gene expression often show marked specificity for tumor cells as compared to normal cells. Taken together, these data encourage clinical evaluation of combination therapies involving epigenetic modulatory drugs and CG antigen-directed tumor vaccines for the treatment of human malignancies.

Original languageEnglish (US)
Pages (from-to)116-120
Number of pages5
JournalEpigenetics
Volume1
Issue number3
DOIs
StatePublished - Jan 1 2006

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Epigenomics
Germ Cells
Vaccines
Antigens
Pharmaceutical Preparations
Neoplasms
Cancer Vaccines
Testicular Neoplasms
Neoplasm Antigens
Histone Deacetylase Inhibitors
Methyltransferases
Gene Silencing
Major Histocompatibility Complex
Tumor Suppressor Genes
Therapeutics
Gene Expression

Keywords

  • 5-aza-2′-deoxycytidine
  • Cancer-testis antigens
  • Cancer/germ-line antigens
  • DNA methylation
  • DNMTs
  • Epigenetics
  • HDAC inhibitors
  • Immune response
  • MAGE-A1
  • NY-ESO-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Potential role for epigenetic modulatory drugs in the enhancement of cancer/germ-line antigen vaccine efficacy. / Karpf, Adam R.

In: Epigenetics, Vol. 1, No. 3, 01.01.2006, p. 116-120.

Research output: Contribution to journalReview article

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