Xenogeneic DNA immunization in melanoma models for minimal residual disease Journal Article


Authors: Hawkins, W. G.; Gold, J. S.; Blachere, N. E.; Bowne, W. B.; Hoos, A.; Lewis, J. J.; Houghton, A. N.
Article Title: Xenogeneic DNA immunization in melanoma models for minimal residual disease
Abstract: 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. © 2001 Elsevier Science.
Keywords: controlled study; treatment outcome; disease-free survival; cancer surgery; cancer recurrence; cancer risk; nonhuman; cancer adjuvant therapy; t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; animal tissue; melanoma; metastasis; skin neoplasms; lung neoplasms; animal experiment; animal model; antineoplastic activity; mice, inbred c57bl; cancer inhibition; lung metastasis; dna; antigens, neoplasm; drug mechanism; cancer vaccines; minimal residual disease; neoplasm, residual; major histocompatibility antigen class 2; cd4-positive t-lymphocytes; dna, neoplasm; immunity; neoplasm transplantation; mouse strain; tumor growth; disease models, animal; therapy; vaccine; major histocompatibility antigen class 1; plasmid dna; immunization; adjuvant; tyrosinase related protein 2; intramolecular oxidoreductases; antigens, heterophile; granulocyte-macrophage colony-stimulating factor; melanosome; provocation test; cancer graft; xenotransplantation; recombinant dna; cancer; female; priority journal; article
Journal Title: Journal of Surgical Research
Volume: 102
Issue: 2
ISSN: 0022-4804
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 2002-02-01
Start Page: 137
End Page: 143
Language: English
DOI: 10.1006/jsre.2001.6302
PUBMED: 11796010
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Jonathan J Lewis
    107 Lewis
  2. William G Hawkins
    18 Hawkins
  3. Axel Hoos
    28 Hoos
  4. Jason Gold
    22 Gold
  5. Wilbur B Bowne
    20 Bowne
  6. Alan N Houghton
    273 Houghton