Antisense compound and method for selectively killing...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/113 (2010.01) A61K 31/7088 (2006.01) A61K 47/48 (2006.01) C07K 14/16 (2006.01) C12N 15/87 (2006.01) C07H 21/00 (2006.01)

Patent

CA 2539972

A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen- activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.

L'invention concerne une méthode et un conjugué permettant de mettre à mort sélectivement des lymphocytes T activés par un antigène. Ledit conjugué contient un composé antisens pratiquement non chargé visant la protéine cFLIP humaine, et un polypeptide TAT inversé (rTAT) couplé de manière covalente au composé antisens. Ce polypeptide rTAT est efficace dans la production d'un prélèvement sélectif du conjugué dans des lymphocytes T activés par un antigène, par rapport au prélèvement du conjugué dans des lymphocytes T non activés. Ce composé antisens cFLIP provoque une mort cellulaire induite par activation de lymphocytes activés. Ladite méthode est utilisée dans le traitement de rejet lors de la transplantation et de troubles auto-immuns.

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