TY  - JOUR
A1  - Ginzkey, Christian
A1  - Eicker, Sven
A1  - Marget, Matthias
A1  - Krause, Jörg
A1  - Brecht, Stefan
A1  - Westphal, Manfred
A1  - Hugo, Heinz-Hermann
A1  - Mehdorn, Maximilian
A1  - Steinmann, Jörg
A1  - Hamel, Wolfgang
T1  - Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen
JF  - Acta Neurochirurgica
N2  - 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.
KW  - lacZ
KW  - rat glioma
KW  - immunotherapy
KW  - DNA vaccination
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126775
VL  - 155
IS  - 1
ER  -