Engraftable neural progenitor and stem cells for brain tumor...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 5/00 (2006.01) C12N 5/0797 (2010.01) A61K 38/00 (2006.01) A61K 48/00 (2006.01) A61K 49/00 (2006.01) C12N 5/10 (2006.01) C12N 15/00 (2006.01) C12Q 1/00 (2006.01) A61K 35/12 (2006.01)

Patent

CA 2313169

One of the impediments to the treatment of some human brain tumors (e.g., gliomas) has been the degree to which they expand, migrate widely, and infiltrate normal tissue. We demonstrate that a clone of multipotent neural progenitor stem cells, when implanted into an experimental glioma, will migrate along with and distribute themselves throughout the tumor in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to express a foreign reporter gene. Furthermore, drawn somewhat by the degenerative environment created just beyond the infiltrating tumor edge, the neural progenitor cells migrate slightly beyond and surround the invading tumor border. When implanted at a distant site from the tumor bed (e.g., into normal tissue, into the contralateral hemisphere, into the lateral ventricles) the donor neural progenitor/stem cells will migrate through normal tissue and specifically target the tumor cells. These results suggest the adjunctive use of neural progenitor/stem cells as a novel, effective delivery vehicle for helping to target therapeutic genes and vectors to invasive brain tumors that have been refractory to treatment.

Un des principaux obstacles au traitement de certaines tumeurs du cerveau chez l'homme (par exemple, des gliomes), est le degré selon lequel ces tumeurs se propagent, migrent fortement et infiltrent les tissus normaux. Selon l'invention, un clone de cellules souches progénitrices neuronales trés puissant, une fois implanté dans le gliome expérimental, va migrer et se répartir dans la tumeur, en juxtaposant les cellules souches qui se propagent fortement, tout en continuant à exprimer un gène reporter étranger. En outre, attirées par l'environnement dégénerescent créé juste au-delà du bord tumoral d'infiltration, les cellules progénitrices neuronales migrent légèrement au-delà et autour de la limite de la tumeur invasive. Une fois implantées au niveau d'un site distant du lit tumoral (par exemple, dans les tissus normaux, dans l'hémisphère contralatérale, dans les ventricules latérales), les cellules souches ou progénitrices neuronales donneuses vont migrer dans le tissu normal et cibler de manière spécifique les cellules tumorales. L'invention traite ainsi de l'utilisation de cellules souches/progénitrices neuronales comme nouveau support d'administration efficace pour faciliter le ciblage des gènes thérapeutiques et des vecteurs pour les tumeurs invasives du cerveau.

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