Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma

Mol Ther. 2007 Nov;15(11):2044-50. doi: 10.1038/ Epub 2007 Aug 28.


Immunity to self antigens on cancer is constrained by tolerance/ignorance. DNA vaccines encoding xenogeneic differentiation antigens, such as tyrosinase (TYR), mediate tumor protection and regression in implantable mouse models, and dogs with spontaneous melanoma. We conducted a trial of mouse and human TYR DNA vaccines in stage III/IV melanoma patients. Eighteen human leukocyte antigen (HLA)-A*0201(+) melanoma patients were randomized as follows: one group received three mouse TYR DNA injections followed by three human TYR DNA injections; the other group received the same vaccines in opposite sequence. The study was conducted at three dose levels: 100, 500, and 1,500 microg DNA/injection, administered intramuscularly (IM) every 3 weeks. Most toxicities were grade 1 injection site reactions. Seven patients developed CD8(+) T-cell responses, defined by a >3 SD increase in baseline reactivity to TYR peptide in tetramer or intracellular cytokine staining (ICS) assays. There was found to be no relationship between dose, assigned schedule, and T-cell response. At a median of 42 months follow-up, median survival has not been reached. Mouse and human TYR DNA vaccines were found safe and induced CD8(+) T-cell responses in 7 of 18 patients. T cells recognizing a native TYR peptide had a phenotype consistent with that of effector memory cells.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies / immunology
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology
  • Drug-Related Side Effects and Adverse Reactions / immunology*
  • Humans
  • Immunogenetics
  • Immunotherapy*
  • Melanoma / genetics
  • Melanoma / immunology*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Mice
  • Middle Aged
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / immunology*
  • Monophenol Monooxygenase / metabolism*
  • Neoplasm Staging
  • Phenotype
  • Survival Rate
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*


  • Antibodies
  • Vaccines, DNA
  • Monophenol Monooxygenase