Recombinant poliovirus for the treatment of cancer

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/41 (2006.01) A61K 35/76 (2006.01) C12N 7/01 (2006.01) C12N 7/04 (2006.01) C12N 15/86 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2346123

The present invention is directed to non-pathogenic, oncolytic, recombinant polioviruses for the treatment of various forms of malignant tumors. The recombinant polioviruses of the invention are those in which the internal ribosomal entry site (IRES) of the wild type poliovirus was exchanged with the IRES of other picornaviruses, and optionally P1, P3 or the 3'NTR thereof was exchanged with that of polivirus Sabin type. More particularly, the present invention is directed to the administration of the non-pathogenic, oncolytic, recombinant poliovirus to the tumor directly, intrathecally or intravenously to cause tumor necrosis. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain. Astounding remissions in experimental animals have been demonstrated for the treatment of malignant glioblastoma multiforme, an almost universally fatal neoplasm of the central nervous system.

La présente invention concerne des poliovirus recombinés non pathogènes oncolytiques destinés au traitement de diverses formes de tumeurs malignes. Les poliovirus recombinés de l'invention sont ceux dans lesquels le site d'entrée ribosomique interne (IRES) du poliovirus de type sauvage a été échangé par l'IRES d'autres picornavirus, et facultativement leur P1, P3 ou 3'NTR a été échangé avec celui d'un poliovirus de type Sabin. Plus particulièrement, la présente invention concerne l'administration du poliovirus recombiné non pathogène oncolytique sur la tumeur directement, par voie intrathécale ou intraveineuse pour provoquer la nécrose des tumeurs. La méthode de la présente invention est particulièrement utile pour le traitement de tumeurs malignes dans divers organes tels que les seins, le colon, le passage bronchique, la muqueuse épithéliale des voies gastro-intestinales, respiratoires supérieures et génito-urinaires, le foie, la prostate et le cerveau. Des rémissions stupéfiantes sur les animaux de laboratoire ont été démontrées pour le traitement du glioblastome malin multiforme, un néoplasme presque universellement mortel du système nerveux central.

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