gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

DNA vaccination against brain tumors expressing lacZ as model antigen

DNA-Vakzinierung gegen Modellantigen-exprimierende Rattengliome

Meeting Abstract

  • C. Ginzkey - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • S. O. Eicker - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • M. Marget - Institut für Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • J. Steinmann - Institut für Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • H. M. Mehdorn - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel
  • corresponding author Wolfgang Hamel - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 05.53

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0336.shtml

Veröffentlicht: 23. April 2004

© 2004 Ginzkey et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Diffusely infiltrating tumors such as gliomas require adjuvant therapies which can cope with this aggressive biological behaviour. Since vaccination represents one such approach we investigated whether DNA vaccination against a model antigen (E. coli lacZ) prior to tumor cell implantation prevents tumor formation in a syngeneic rat gliosarcoma model.

Methods

Fisher 344 rats were vaccinated thrice in weekly intervals via the intramuscular route with an expression plasmid encoding lacZ or an empty control plasmid, and plasmids encoding putative adjuvants were added in some animals. Following vaccination, 9LlacZ cells were implanted into the striatum. After three weeks brains were removed after splencectomy and frozen in liquid nitrogen for assessment of tumor size and immunohistochemical studies.

Results

Vaccination without plasmid or with the control plasmid resulted in the formation of large tumors (183.7 mm3 ±99.2; mean ±standard deviation). In lacZ vaccinated animals tumors were significantly smaller (18.9 mm3 ±13.3). Co-injection of expression plasmids encoding interleukin-12 (59.2 mm3 ±24.6) or flt-3 ligand (69.2 mm3 ±40.6) did not have an adjuvant effect but resulted in the formation of larger tumors. All tumors were heavily infiltrated with CD8+ cells and less with NK cells, but only a minority expressed activation markers (CD25+ and perforin, respectively). Tumors were also infiltrated with non-actived microglial cells (ED-1 negative). Cytotoxic T cells generated from restimulated spleen preparations (CTL assay) revealed target cell lysis of >50% in some lacZ vaccinated animals which was specific for 9LlacZ as well as wild-type 9L target cells whereas another syngeneic cell line (MADB 106) was not lysed. In control vaccinated animals, lysis rates remained below 25%. This is consistent with higher IFN-γ production in lymphocytes of lacZ vaccinated animals compared to control vaccinated animals as determined by the ELISPOT assay. However, both in vitro-assays did not correlate with tumor size.

Conclusions

Effective but incomplete inhibition of tumor formation following DNA vaccination has been demonstrated in a syngeneic rat gliosarcoma model. This model is suited for further investigations related to more effective adjuvants and the immunological mechanisms involved.