Self-deleting vectors for cancer therapy

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/85 (2006.01) A61K 38/43 (2006.01) A61K 38/45 (2006.01) A61K 38/46 (2006.01) A61K 48/00 (2006.01) C12N 15/63 (2006.01) C12N 15/867 (2006.01)

Patent

CA 2305655

The invention relates to vectors for cancer therapy which as a result of genetic differences between normal and transformed cells selectively eliminate the latter. This is made possible by integrating a sequence-specific recombinase into a viral or non-viral expression vector, whose expression is controlled by a transcription factor which has mutated in tumour cells and is therefore inactive, as well as by a suicide gene which is flanked by at least one recombinase-specific target sequence. Through the transcription-factor-mediated activation of the sequence-specific recombinase the vector is eliminated from untransformed cells together with the suicide gene. The vector is, however, not eliminated from tumour cells in which the transcription factor is not active and expresses the suicide gene in said cells. After contact with a corresponding prodrug these cells are selectively killed off.

L'invention concerne des vecteurs s'utilisant dans le traitement de cancers, qui en raison de différences génétiques entre des cellules normales et des cellules transformées, éliminent ces dernières de manière sélective. Cette opération est possible par intégration d'une recombinase séquence-spécifique dans un vecteur d'expression viral ou non viral, dont l'expression est contrôlée par un facteur de transcription muté dans des cellules tumorales et par conséquent non actif, ainsi que par l'utilisation d'un gène suicide flanqué d'au moins une séquence cible recombinase-spécifique. L'activation de la recombinase séquence-spécifique, induite par le facteur de retranscription permet d'éliminer hors des cellules non transformées, le vecteur conjointement avec le gène suicide. Par contre, le vecteur n'est pas éliminé de cellules tumorales où le facteur de transcription n'est pas actif et ledit vecteur exprime le gène suicide. Ces cellules sont tuées de manière sélective après contact avec un promédicament approprié.

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