Die Wirkung von zerebral exprimiertem Interleukin-12 auf die Gliomentwicklung ineinem transgenes Mausmodell
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Philipps-Universität Marburg
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Abstract
This thesis examines the effect of interleukin-12 (IL-12) on a murine stereotactically implanted brain tumor.
It has already been demonstrated in a number of tumor models that IL-12 inhibits
tumor growth. This could also be demonstrated to some extent in humans.
A tumor model was established in which 3x104 GL261 type glioma cells were implanted stereotactically into the cerebellum of laboratory mice. The effect of transgenically expressed interleukin-12 in the cerebellum was examined in laboratory mice which over-expressed IL-12 and, for reasons of comparison, in wild-type animals.
Literature describes numerous models which deliver interleukin-12 to the organism externally via viruses, gene gun, naked DNA injection or subcutaneous injection. In our model we examined endogenous over-expression of IL-12 in the cerebellum.
Our results showed that GF-IL 12 tg laboratory animals had markedly fewer symptoms than wild-type animals. On average, tumor volumes in the GF-IL 12 tg laboratory animals were 64% smaller than in the wild-type animals. This was statistically significant.
(p ≤ 0.0013, Mann Whitney U-Test).
In immunohistochemical tests, we demonstrated that CD8+ T-cells, in particular, had infiltrated tumor tissue in GF-IL 12 tg laboratory animals. Later depletion experiments underlined the key role of the CD8+ T-cells. We were also able to demonstrate the suppressor function of CD4+ T-cells on CD8+ cells. We examined the role of NKcells, which have a subordinate role in this model, using CRAG animals. Finally, using IFN-gamma KO animals, we were able to show that IFN-gamma is not necessary for recruitment of CD8+ T-cells and tumor rejection.
Even today, surgical resection followed by chemotherapy and radiotherapy remains
the standard therapy for malignant gliomas. Immunotherapy with IL-12 could improve courses here. This thesis shows the fundamental ways in which endogenous IL-12 production mediates tumor rejection. IL-12 therapies of malignant gliomas in humans are still at the trial stage, however.
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Created: 2008Issued: 2009-05-06Updated: 2011-08-10
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Brain tumorInterleukin 12
DFG-subjects
Interleukin 12Hirntumor
DDC-Numbers
610
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Vetter, Marcus (138161577): Die Wirkung von zerebral exprimiertem Interleukin-12 auf die Gliomentwicklung ineinem transgenes Mausmodell. : Philipps-Universität Marburg 2009-05-06. DOI: https://doi.org/10.17192/z2009.0108.
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This item has been published with the following license: In Copyright