@article{GinzkeyEickerMargetetal.2013, author = {Ginzkey, Christian and Eicker, Sven and Marget, Matthias and Krause, J{\"o}rg and Brecht, Stefan and Westphal, Manfred and Hugo, Heinz-Hermann and Mehdorn, Maximilian and Steinmann, J{\"o}rg and Hamel, Wolfgang}, title = {Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen}, series = {Acta Neurochirurgica}, volume = {155}, journal = {Acta Neurochirurgica}, number = {1}, doi = {10.1007/s00701-012-1526-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126775}, pages = {51-59}, year = {2013}, 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. Conclusion 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.}, language = {en} }