Htlv-i tax induced killing of p53 null cancer cells

Details Htlv-i tax induced killing of p53 null cancer cells Htlv-i tax induced killing of p53 null cancer cells

A - Human Necessities

61

K

A61K 48/00 (2006.01) A61K 31/7088 (2006.01) A61N 5/00 (2006.01) A61P 35/02 (2006.01) C07K 14/15 (2006.01) C12N 5/00 (2006.01) C12N 15/867 (2006.01)

Patent

CA 2486327

This invention is based on the finding that expression of an exogenous nucleic acid encoding a polypeptide having human T-cell leukemia virus type I (HTLV-1) Tax activity in p53 null cells results in a sensitization of those cells to DNA damaging agents. Therefore, the present invention is directed to a method of inducing cell death in p53 null cells, enhancing susceptibility to such DNA damaging agents, and the selective cell killing of p53 null cells. It has been found that retroviral vectors, and particularly lentiviral vectors, are suitable for the present invention to permit the transient expression of the HTLV-1 Tax protein in the p53 null cells, which sensitizes the cells.

On a découvert que l'expression d'un acide nucléique exogène codant pour un polypeptide qui présente une activité de la protéine Tax du virus de la leucémie T humaine de type 1 I (HTLV-1) dans des lymphocytes nuls p53 entraîne la sensibilisation de ces cellules à des agents détériorant de l'ADN. En conséquence, l'invention concerne une méthode permettant d'induire la mort cellulaire dans les lymphocytes nuls p53, ce qui permet d'améliorer leur susceptibilité aux agents détériorant l'ADN, et de détruire sélectivement des lymphocytes nuls p53. On a découvert que des vecteurs rétroviraux, et en particulier des vecteurs lentiviraux, permettent, de manière appropriée, l'expression transitoire de la protéine Tax de HTLV-1 dans les lymphocytes nuls, ce qui sensibilise lesdites cellules.

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