Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen
- Christian GinzkeyAffiliated withDepartment of Neurosurgery, University of Schleswig-HolsteinDepartment of Oto-Rhino-Laryngology, Julius-Maximilian-University
- , Sven EickerAffiliated withDepartment of Neurosurgery, University of Schleswig-HolsteinDepartment of Neurosurgery, Heinrich-Heine-University
- , Matthias MargetAffiliated withInstitute of Immunology, University of Schleswig-Holstein
- , Jörg KrauseAffiliated withDepartment of Neurosurgery, University of Schleswig-Holstein
- , Stefan BrechtAffiliated withInstitute of Pharmacology, University of Schleswig-Holstein
- , Manfred WestphalAffiliated withDepartment of Neurosurgery, University Hospital Hamburg-EppendorfKlinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf
- , Heinz-Hermann HugoAffiliated withDepartment of Neurosurgery, University of Schleswig-Holstein
- , Maximilian MehdornAffiliated withDepartment of Neurosurgery, University of Schleswig-Holstein
- , Jörg SteinmannAffiliated withInstitute of Immunology, University of Schleswig-Holstein
- and 1 more
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).
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.
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.
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.
KeywordsDNA vaccination Immunotherapy Rat glioma lacZ
- Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen
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Volume 155, Issue 1 , pp 51-59
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- 1. Department of Neurosurgery, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
- 4. Department of Oto-Rhino-Laryngology, Julius-Maximilian-University, Würzburg, Germany
- 5. Department of Neurosurgery, Heinrich-Heine-University, Düsseldorf, Germany
- 2. Institute of Immunology, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
- 3. Institute of Pharmacology, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
- 6. Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
- 7. Klinik für Neurochirurgie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany