title: Tumor endothelial marker 8 enhances tumor immunity in conjunction with immunization against differentiation Ag.
abstract: BACKGROUND
  We have previously shown that xenogeneic DNA vaccines encoding rat neu and melanosomal differentiation Ag induce tumor immunity. Others have developed vaccines targeting tumor neovasculature. Tumor endothelial marker 8 (TEM8) is expressed in the neovasculature of human tumors, and in the mouse melanoma B16, but its expression is limited in normal adult tissues. We describe a DNA vaccine combining xenogeneic tumor Ag and TEM8.
  
  
  METHODS
  In-situ hybridization was used to detect TEM8 RNA in mouse tumors. Mice transgenic for the rat neu proto-oncogene were immunized with DNA vaccines encoding TEM8 and the extracellular domain of rat neu and challenged with the 233-VSGA1 breast cancer cell line. In parallel experiments, C57BL/6 mice were immunized with TEM8 and human tyrosinase-related protein 1 (hTYRP1/hgp75) and challenged with B16F10 melanoma.
  
  
  RESULTS
  TEM8 was expressed in the stroma of transplantable mouse breast and melanoma tumors. In both model systems, TEM8 DNA had no activity as a single agent but significantly enhanced the anti-tumor immunity of neu and hTYRP1/hgp75 DNA vaccines when given in concert. The observed synergy was dependent upon CD8+ T cells, as depletion of this cell population just prior to tumor challenge obviated the effect of the TEM8 vaccine in both tumor models.
  
  
  CONCLUSIONS
  A local immune response to TEM8 may increase inflammation or tumor necrosis within the tumor, resulting in improved Ag presentation of HER2/neu and hTYRP1/hgp75. Alternatively, TEM8 expression in host APC may alter T-cell interactions or homing. In this way, TEM8 may act more as an adjuvant than an immunologic target.
authors.affiliation: Swim Across America Laboratory of Tumor Immunology, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: P
authors.initials: P
authors.lastname: Felicetti
authors.forename: M
authors.initials: M
authors.lastname: Mennecozzi
authors.forename: A
authors.initials: A
authors.lastname: Barucca
authors.forename: S
authors.initials: S
authors.lastname: Montgomery
authors.forename: F
authors.initials: F
authors.lastname: Orlandi
authors.forename: K
authors.initials: K
authors.lastname: Manova
authors.forename: A N
authors.initials: AN
authors.lastname: Houghton
authors.forename: P D
authors.initials: PD
authors.lastname: Gregor
authors.forename: A
authors.initials: A
authors.lastname: Concetti
authors.forename: F M
authors.initials: FM
authors.lastname: Venanzi
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D004273:DNA, Neoplasm / Q000276:immunology; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D010088:Oxidoreductases / Q000276:immunology; D000090063:Proto-Oncogene Mas; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D000943:Antigens, Differentiation; D019496:Cancer Vaccines; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D010088:Oxidoreductases; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA; C000715470:MAS1 protein, human; C489799:TYRP1 protein, human