RNA INTERFERENCE THAT BLOCKS EXPRESSION OF PRO-APOPTOTIC PROTEINS POTENTIATES IMMUNITY INDUCED BY DNA AND TRANSFECTED DENDRITIC CELL VACCINES

摘要

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