Antisense therapy for hormone-regulated tumors

Details Antisense therapy for hormone-regulated tumors Antisense therapy for hormone-regulated tumors

C - Chemistry, Metallurgy

12

N

C12N 15/11 (2006.01) A61K 31/7088 (2006.01) A61P 35/00 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2375467

A method is provided for treating hormone-regulated tumors (for example, breast and prostatic tumors) in mammals, including humans, by administration of an antisense ODN which is complementary to a portion of the gene encoding IGFBP-5. Using the Shionogi tumor model in vitro and in vivo, the administration of such an ODN was shown to reduce proliferation of tumor cells, and also to delay the progression to androgen independence. Thus, treatment of prostate cancer in mammals, including humans, and delay of the progression of prostate tumors to androgen independence is accomplished by administering to the mammal a therapeutically effective amount of an antisense oligodeoxynucleotide which is complementary to a portion of the nucleic acid sequence encoding IGFBP-5 and which hybridizes with such a sequence to inhibit expression of IGFBP-5. Specific antisense ODN's which are suitable for use in the method are GACCACGCTGATCACCAT (Seq. ID. No. 1), which is derived from the murine gene sequence, and CGCGGTGAGCAACACCAT (Seq. ID. No. 3) and AGGTCATGCAGCAGCCGC (Seq. ID No 4), which are derived from the human gene sequence.

L'invention concerne une méthode de traitement de tumeurs à régulation hormonale (par exemple, des tumeurs du sein et de la prostate) chez des mammifères, notamment chez des sujets humains, par administration d'un ODN (oligodésoxynucléotide) antisens lequel est complémentaire à une partie du gène codant IGFBP-5. A l'aide du modèle de tumeur Shionogi in vitro et in vivo, l'administration de cet ODN a montré une réduction de la prolifération des cellules tumorales et également a permis de différer la progression vers l'indépendance androgénique. Ainsi, le traitement du cancer de la prostate chez des mammifères, notamment des sujets humains, et le retard de la progression de tumeurs de la prostate vers l'indépendance androgénique sont obtenus par administration au mammifère d'une dose thérapeutique efficace d'un oligodésoxynucléotide antisens lequel est complémentaire d'une partie de la séquence d'acide nucléique codant IGFBP-5 et lequel s'hybride à cette séquence pour inhiber l'expression d'IGFBP-5. Les ODN antisens spécifiques adaptés à une utilisation dans la méthode sont GACCACGCTGATCACCAT (Seq. ID. No. 1), laquelle est dérivée de la séquence de gènes murins, et CGCGGTGAGCAACACCAT (Seq. ID No. 3) et AGGTCATGCAGCAGCCGC (Seq. ID No. 4), lesquelles sont dérivées de la séquence de gènes humains.

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