A simple method to cure established tumors by inflammatory killing of normal cells

Gregory A. Daniels, Luis Sanchez-Perez, Rosa Maria Diaz, Timothy Kottke, Jill Thompson, Maoyi Lai, Michael Gough, Mahzuz Karim, Andrew Bushell, Heung Chong, Alan Melcher, Kevin Harrington, Richard G. Vile

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

We describe a simple technology used to cure an established metastatic disease. Intradermal injection of plasmid DNA encoding a transcriptionally targeted cytotoxic gene, along with hsp70, not only promoted tissue-specific, inflammatory killing of normal melanocytes, but also induced a CD8+ T-cell-dependent, antigen-specific response in mice that eradicated systemically established B16 tumors. This CD8+ T cell response was subsequently suppressed in vivo within a few days. The data demonstrate that deliberate destruction of normal tissue can be exploited to generate immunity against a malignant disease originating from that tissue. This approach obviates the need to identify tumor antigens and does not require complex isolation of tumor cells or their derivatives. In addition, it provides a model system for studying the mechanisms underlying the etiology and control of autoimmune diseases. Finally, despite targeting normal tissue, therapy could be separated from development of overt autoimmune symptoms, suggesting that the strategy may be valuable against tumors derived from both non-essential and essential tissue types.

Original languageEnglish (US)
Pages (from-to)1125-1132
Number of pages8
JournalNature biotechnology
Volume22
Issue number9
DOIs
StatePublished - Sep 2004

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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  • Cite this

    Daniels, G. A., Sanchez-Perez, L., Diaz, R. M., Kottke, T., Thompson, J., Lai, M., Gough, M., Karim, M., Bushell, A., Chong, H., Melcher, A., Harrington, K., & Vile, R. G. (2004). A simple method to cure established tumors by inflammatory killing of normal cells. Nature biotechnology, 22(9), 1125-1132. https://doi.org/10.1038/nbt1007