title: Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen.
abstract: BACKGROUND
  Vaccination against tumour-associated antigens is one approach to elicit anti-tumour responses. We investigated the effect of polynucleotide (DNA) vaccination using a model antigen (E. coli lacZ) in a syngeneic gliosarcoma model (9L).
  
  
  METHODS
  Fisher 344 rats were vaccinated thrice by intramuscular injection of a lacZ-encoding or a control plasmid in weekly intervals. One week after the last vaccination, lacZ-expressing 9L cells were implanted into the striatum.
  
  
  RESULTS
  After 3 weeks, in lacZ-vaccinated animals the tumours were significantly smaller than in control-vaccinated animals. In cytotoxic T cell assays lysis rates of >50 % could only be observed in a few of the lacZ-vaccinated animals. This response was directed against lacZ-expressing and parental 9L cells but not against syngeneic MADB 106 adenocarcinoma cells. In Elispot assays interferon-γ production was observed upon stimulation with 9LlacZ and 9L wild-type but not MADB 106 cells. This response was higher for lacZ-immunized animals. All animals revealed dense infiltrates with CD8+ lymphocytes and, to a lesser extent, with NK cells. CD25-staining indicated cells possibly associated with the maintenance of peripheral tolerance to self-antigens. All tumours were densely infiltrated by microglia consisting mostly of ramified cells. Only focal accumulation of macrophage-like cells expressing ED1, a marker for phagocytic activity, was observed.
  
  
  CONCLUSIONS
  Prophylactic DNA vaccination resulted in effective but incomplete suppression of brain tumour formation. Mechanisms other than cytotoxic T cell responses as measured in the generally used in vitro assays appear to play a role in tumour suppression.
authors.affiliation: Department of Neurosurgery, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ginzkey
authors.forename: Sven
authors.initials: S
authors.lastname: Eicker
authors.forename: Matthias
authors.initials: M
authors.lastname: Marget
authors.forename: Jörg
authors.initials: J
authors.lastname: Krause
authors.forename: Stefan
authors.initials: S
authors.lastname: Brecht
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Heinz-Hermann
authors.initials: HH
authors.lastname: Hugo
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mehdorn
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hamel
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001932:Brain Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D019496:Cancer Vaccines; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology; D018316:Gliosarcoma / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D019444:Vaccines, DNA; D001616:beta-Galactosidase / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D019496:Cancer Vaccines; D019444:Vaccines, DNA; D001616:beta-Galactosidase