An epigenetically altered tumor cell vaccine

Cancer Immunol Immunother. 2004 Aug;53(8):748-54. doi: 10.1007/s00262-004-0513-0. Epub 2004 Feb 28.


Functional inactivation of genes critical to immunity may occur by mutation and/or by repression, the latter being potentially reversible with agents that modify chromatin. This study was constructed to determine whether reversal of gene silencing, by altering the acetylation status of chromatin, might lead to an effective tumor vaccine. We show that the expression of selected genes important to tumor immunity, including MHC class II, CD40, and B7-1/2 are altered by treating tumor cells in vitro with a histone deacetylase inhibitor, trichostatin A (TSA). Tumor cells treated in vitro with TSA showed delayed onset and rate of tumor growth in 70% of the J558 plasmacytoma and 100% of the B16 melanoma injected animals. Long-term tumor specific immunity was elicited to rechallenge with wild-type cells in approximately 30% in both tumor models. Splenic T cells from immune mice lysed untreated tumor cells, and SCID mice did not manifest immunity, suggesting that T cells may be involved in immunity. We hypothesize that repression of immune genes is involved in the evasion of immunity by tumors and suggest that epigenetically altered cancer cells should be further explored as a strategy for the induction of tumor immunity.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism
  • Cancer Vaccines / therapeutic use*
  • Cell Division / immunology
  • Enzyme Inhibitors / therapeutic use
  • Genes, MHC Class I / drug effects*
  • Genes, MHC Class II / drug effects*
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Histone Deacetylase Inhibitors
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / prevention & control
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / prevention & control
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Plasmacytoma / immunology*
  • Plasmacytoma / prevention & control
  • Spleen / immunology
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • CD86 protein, human
  • Cancer Vaccines
  • Cd86 protein, mouse
  • Enzyme Inhibitors
  • Histocompatibility Antigens Class II
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Membrane Glycoproteins
  • trichostatin A