Modification of Professional Antigen-Presenting Cells with Small Interfering RNA (siRNA) Targeting BAK and/or BAX Can Enhance DNA Vaccine Potency

dendritic cell survival by co-administering DNA encoding antigen with DNA encoding inhibitors of apoptosis to DCs. We previously tested a variety of anti-apoptotic factors for their ability to enhance DC survival and antigen -specific CD8+ T cell immune responses when co-administered with DNA encoding antigen. Because intracellular targeting and anti-apoptotic strategies modify DCs via different mechanisms, we have been able to combine anti-apoptotic strategies for prolonging DC life with intracellular targeting strategies for enhancing MHC class I and II presentation of antigen by DCs to improve DNA vaccine potency. While coadministration of DNA encoding antigen with DNA encoding anti-apoptotic proteins can significantly enhance DNA vaccine potency, the use of DNA encoding anti-apoptotic proteins (such as Bcl-2) raises significant concerns related to oncogenicity. Recently we have developed a relatively new technology using small interfering RNA (siRNA) that may provide similar effects while alleviating concerns for oncogenicity. RNA interference (RNAi) using siRNA has been shown to be an effective means of silencing gene expression in cells. We showed that the coadministration of DNA vaccines encoding antigen with siRNA targeting key pro-apoptotic proteins prolongs the lives of antigen-expressing dendritic cells in the draining lymph nodes, enhances antigen-specific CD8+ T cell responses, and elicits potent antitumor effects in vaccinated mice. Our data indicate that employment of siRNA targeting pro-apoptotic proteins to modify the properties of professional antigen-presenting cells in vivo represents a plausible strategy for enhancing vaccine potency. Vaccines for the treatment of cancer and infectious disease. Patent (Set) WO 2006/073970

Inventor(s): Wu, T.C.

Type of Offer: Licensing



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