A simple method to cure established tumors by inflammatory killing of normal cells.
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.
Daniels
Gregory A
GA
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Sanchez-Perez
Luis
L
Diaz
Rosa Maria
RM
Kottke
Timothy
T
Thompson
Jill
J
Lai
Maoyi
M
Gough
Michael
M
Karim
Mahzuz
M
Bushell
Andrew
A
Chong
Heung
H
Melcher
Alan
A
Harrington
Kevin
K
Vile
Richard G
RG
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007114:Immunization / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016019:Survival Analysis; D013937:Thymidine Kinase / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D014764:Viral Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D000941:Antigens; D014764:Viral Proteins; C099241:thymidine kinase, Canid herpesvirus 1; D013937:Thymidine Kinase