Grant: Project Grant

Therapeutic vaccines are currently being researched as a treatment for cancer. This approach aims to stimulate adaptive immunity against tumors by delivering antigens derived from the tumor cells, along with adjuvant molecules that enhance the immune response to the antigens. A major roadblock in the success of this therapeutic approach is the ineffective co-delivery of the antigen and adjuvant to the lymph node, where such immune responses are orchestrated. Nucleic acids are a potent class of adjuvants, but they do not accumulate effectively in lymph nodes and are degraded rapidly by endogenous nucleases. Additionally, they differ significantly in size and chemistry from tumor derived peptide antigens, and therefore exhibit different pharmacokinetics and biodistribution. This project will use DNA nanotechnology to convert nucleic acid adjuvants into self-assembling nanoparticles with controlled shape and size, which has been shown to drain effectively into lymph nodes. Additionally, we have discovered polymer and peptide chemistries that protect these nanostructures from enzymatic degradation, and allow for direct display of peptide antigens on the nanostructures. We will study the influence of peptide and polymer design on the in vivo co-delivery of vaccine components to dendritic cells within the lymph nodes. We will measure accumulation of vaccine components at the cellular and tissue levels, as well as immune responses as a function of these designs. Finally, we will quantify the ability of this vaccine to elicit antigen-specific cellular immunity.