Rna interference that blocks expression of pro-apoptotic...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01)

Patent

CA 2594040

An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and/or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC~s transfected with siRNA targeting Bak and/or Bax serve as improved immunogens and tumor immunotherapeutic agents.

L'invention concerne une stratégie immunothérapeutique combinant des compositions de vaccins ADN à codage antigène combinées à un siARN dirigé vers des gènes pro-apoptotiques, principalement Bak et Bax, dont les produits sont connus comme conduisant à une mort apoptotique. L'injection de gènes par le pistolet à gènes (bombardement de particules) de siARN, spécifique de Bak et/ou Bax pour des cellules dendritiques (CD) d'expression antigène, prolonge les vies de telles cellules dendritiques (CD) et conduit à une génération améliorée de réponses immunes in vivo occasionnées par des cellules CD8 + T spécifiques d'antigènes. De la même façon, des CD chargées d'antigènes transfectés avec Bak et/ou Bax de ciblage siARN servent d'immunogènes améliorés et d'agents immunothérapeutiques des tumeurs.

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