Tcf responsive element

Details Tcf responsive element Tcf responsive element

C - Chemistry, Metallurgy

12

N

C12N 15/12 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) A61P 35/00 (2006.01) C07K 14/47 (2006.01) C12N 9/02 (2006.01) C12N 15/53 (2006.01) C12N 15/66 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2401533

Disclosed are DNA elements and constructs useful for obtaining tumour- selective gene expression in tumours having a mutated .beta.-catenin/APC pathway. In particular, the use of these constructs to express genes encoding therapeutic proteins in colorectal cancer cells is described. The constructs comprise multiple repeats of a TCF-binding element operably linked to a promoter. By means of such a construct, tumour cell-specific expression of a prodrug-converting enzyme such as nitroreductase may be achieved. Coupled with systemic administration of a suitable prodrug, such as CB1954, selective killing of such tumour cells can be demonstrated.

La présente invention concerne des éléments et des constructions d'ADN, qui sont utilisés afin d'obtenir une expression génique à sélectivité tumorale dans des tumeurs présentant une voie .beta.-caténine/polypose recto-colique familiale (APC) mutée. Cette invention concerne notamment l'utilisation de ces constructions, afin d'exprimer des gènes codant des protéines thérapeutiques dans des cellules cancéreuses colorectales. Ces constructions comprennent plusieurs répétitions d'un élément se liant au facteur de transcription de lymphocytes T (TCF), qui est relié de manière opérationnelle à un promoteur. Une telle construction permet d'assurer l'expression spécifique aux cellules tumorales d'une enzyme se transformant en promédicament, telle que la nitroréductase. Associée à l'administration systématique d'un promédicament adapté, tel que CB1954, l'élimination sélective de telles cellules tumorales peut être mise en évidence.

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