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Validation of a targeted adenoviral vector efficiently and safely expressing a therapeutic gene in glioblastoma in murine models

An adenoviral vector is being evaluated for its efficient and safe therapeutic effect in a model of murine glioblastoma. We generated HC-Ad vectors expressing either the reporter EGFP or the molecule PEDF, which has potent anti-angiogenic activity and which we previously tested in an eye model of neoangiogenesis. In collaboration with the Department of Neurology, University of Tubingen, we have started testing these two vectors in murine models of brain cancer. One approach is based on the intracranial LN229 model in CD1 nude mice.

Another approach is based on ex vivo gene transfer into normal carrier cells that will then migrate to the tumour. In proof-of-concept experiments we engrafted F98 rat glioblastoma cells into the right caudatoputamen. Tumours were allowed to develop for 1 week, before 50000 glial restricted precursor cells or ES cell-derived precursor cells were transplanted into the corpus callosum of the left hemisphere. One week later the animals were sacrificed and EGFP expressing cells were counted every 10th serial section of the brains. Interestingly, both glial as well as neural precursor cells migrated to the tumour to contra-lateral hemisphere. After arrival at the bumot, both cell types surrounded and even evaded the tumour. In future experiments we will analyse, whether tumour-inhibitory effects can be observed, if the transplanted cells are loaded with HC-Ad vectors expressing potentially therapeutic molecules including PEDF.

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University of Ulm
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89081 Ulm
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