Xenogeneic DNA immunization in melanoma models for minimal residual disease

J Surg Res. 2002 Feb;102(2):137-43. doi: 10.1006/jsre.2001.6302.


Introduction: DNA immunization with xenogeneic genes encoding homologous antigens protects mice against tumor challenge with syngeneic melanoma in a lung metastasis model. The effect of xenogeneic human TRP-2 (hTRP2) DNA immunization on disease confined to an orthotopic site, the skin, and in a model of minimal residual disease that is relevant to a setting of adjuvant therapy for micrometastatic cancer is reported.

Methods: Immunization and tumor challenge with B16F10LM3 melanoma were performed in C57BL/6 mice and in mice genetically deficient in MHC class I or II molecules. A melanoma variant of B16 with a predilection for lung metastasis was selected and used to challenge C57BL/6 mice. Tumor challenge in the footpad with the B16 variant was followed by local tumor growth and lung metastasis. The tumor-bearing distal extremities were surgically resected and mice were randomized to receive hTRP2 DNA immunization or no treatment. Approximately 3-5 weeks after surgical resection, lungs were harvested and metastases counted.

Results: Xenogeneic DNA immunization with hTRP2 prevented tumor growth in the skin by a mechanism requiring CD4(+) and CD8(+) T cells but did not inhibit the growth of established tumors. Adjuvant immunization with hTRP2 DNA after resection significantly reduced lung metastases and decreased local recurrence rates after surgical resection.

Conclusions: Xenogeneic DNA immunization with hTRP2 was effective in protecting mice from intradermal tumor challenge. Immunization prevented local recurrence and the development of metastases in a mouse model of minimal residual disease, supporting a role for DNA immunization against melanosomal antigens as an adjuvant to surgery in high-risk primary melanomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Heterophile / pharmacology*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / pharmacology*
  • DNA, Neoplasm / immunology
  • Disease Models, Animal
  • Disease-Free Survival
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Immunization / methods
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / immunology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasm, Residual / immunology
  • Neoplasm, Residual / pathology
  • Neoplasm, Residual / prevention & control*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / prevention & control*
  • Skin Neoplasms / secondary


  • Antigens, Heterophile
  • Antigens, Neoplasm
  • Cancer Vaccines
  • DNA, Neoplasm
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Intramolecular Oxidoreductases
  • dopachrome isomerase