Cea/nca-based differentiation cancer therapy

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/11 (2006.01) C07K 14/705 (2006.01) C07K 16/30 (2006.01) G01N 33/50 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2319098

The present invention relates to a novel cancer therapy based on interference with the function or on downregulation of overproduced CEA/NCA, which plays an instrumental role in tumorigenesis and malignant progression through its differentiation-blocking activity. More precisely, there is provided three short amino acid sequence subdomains in the N domain of CEA and NCA that, when applied as peptides, peptide mimetics or anti-subdomain monoclonal antibodies to malignant tumors overproducing CEA/NCA, induce them to differentiate, thereby inhibiting their ability to grow and increasing the efficacy of other modes of treatment. Four other means of releasing the CEA/NCA-imposed differentiation block are also provided. The enhanced differentiation status of cancers induced by these CEA/NCA-based novel modes of treatment is expected to increase the efficacy of virtually any other mode of treatment by enhancing the bystander effect, whereby more differentiated cancer cells normalize the behavior of adjacent less differentiated cancer cells.

La présente invention porte sur une nouvelle thérapie anticancéreuse basée sur l'interférence avec la fonction ou sur la rétro-régulation de CEA/NCA en surproduction qui joue un rôle instrumental dans l'action tumorigène et l'évolution maligne par son activité bloquant la différenciation. Plus précisément, l'invention porte sur trois sous-domaines de séquences courtes d'acides aminés du domaine N de CEA et NCA qui, appliqués sous forme de peptides, mimétiques peptidiques ou anticorps monoclonaux anti-sous-domaines sur des tumeurs malignes surproductrices de CEA/NCA, les induisent à se différencier, ce qui inhibent leur capacité à se développer et à accroître l'efficacité d'autres modes de traitement. L'invention porte également sur quatre autres moyens de libérer le bloc de différentiation imposé par CEA/NCA. On peut s'attendre à ce que l'état de différenciation amélioré des cancers induits par ces nouveaux modes de traitement à base de CEA/NCA augmentent virtuellement l'efficacité de tout autre mode de traitement en renforçant l'effet du témoin, plusieurs cellules cancéreuses différenciées normalisant le comportement des cellules cancéreuses adjacentes moins différenciées.

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