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An epigenetically altered tumor cell vaccine

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Abstract

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.

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Fig. 1
Fig. 2A–D
Fig. 3A,B

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Abbreviations

APCs:

antigen-presenting cells

CIITA:

MHC class II transactivator

CTLs:

cytotoxic T lymphocytes

HDACs:

histone deacetylases

LPAM:

L-phenylalanine mustard

TSA:

trichostatin A

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Acknowledgements

We thank Elizabeth A. Repasky and Protul Shrikant for critical review of the manuscript.

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Authors and Affiliations

  1. Laboratory of Molecular Medicine, Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

    A. Nazmul H. Khan, William J. Magner & Thomas B. Tomasi

  2. Department of Medicine, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14214, USA

    Thomas B. Tomasi

  3. Department of Microbiology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14214, USA

    William J. Magner & Thomas B. Tomasi

Authors
  1. A. Nazmul H. Khan
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  2. William J. Magner
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  3. Thomas B. Tomasi
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Corresponding author

Correspondence to Thomas B. Tomasi.

Additional information

This work was supported by grant HD 17013 from the National Institutes of Health, and utilized core facilities supported in part by RPCI’s NCI Cancer Support Grant CA16056.

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Khan, A.N.H., Magner, W.J. & Tomasi, T.B. An epigenetically altered tumor cell vaccine. Cancer Immunol Immunother 53, 748–754 (2004). https://doi.org/10.1007/s00262-004-0513-0

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  • DOI: https://doi.org/10.1007/s00262-004-0513-0

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