Nature Biotechnology
22, 1125 - 1132 (2004)
Published online: 1 August 2004; Corrected online: 15 August 2004 | doi:10.1038/nbt1007
A simple method to cure established tumors by inflammatory killing of normal cellsGregory A Daniels1, 2, 8, Luis Sanchez-Perez1, 3, 8, Rosa Maria Diaz1, 3, Timothy Kottke1, Jill Thompson1, Maoyi Lai1, Michael Gough1, 3, Mahzuz Karim4, Andrew Bushell4, Heung Chong5, Alan Melcher6, Kevin Harrington7
& Richard G Vile1, 21
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA. 2
Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. 3
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA. 4
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom. 5
Department of Pathology, St. George's Hospital Medical School, Tooting, London, UK. 6
CRUK Oncology Unit, St. James' Hospital, Leeds, UK. 7
Chester Beatty Laboratories, Fulham Road, London, UK. 8
These authors contributed equally to this work.
Correspondence should be addressed to Richard G Vile vile.richard@mayo.eduWe 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.
*Note: In the version of this article originally published online, the name of one of the authors was spelled incorrectly. Mayoi Lai should be Maoyi Lai. This mistake has been corrected in the HTML version and will appear correctly in print.
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