Novel Delivery Systems for RNA-based Cancer Vaccines

Fast-Track proposals will NOT be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 2-4 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,250,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary The number of RNA-based cancer vaccines under development is rapidly expanding as genomic and predictive approaches reveal novel (neo)antigens capable of eliciting an immune response. While the rules for optimizing antigen selection are not yet fully understood, RNA-based vaccines can be generated quickly and have the flexibility to incorporate multiple (neo)antigens. These features make RNA-based vaccines ideally suited for rapid development and testing, as well as generating personalized cancer vaccines designed to elicit a tumor-specific response in an individual patient. While additional work is needed to demonstrate that RNA-based vaccines are safe and effective as anti-cancer agents, research in this field is evolving rapidly. A critical step in developing an RNA-based vaccine is selecting an appropriate delivery system that can be produced at scale to generate clinical grade material. Lipid nanoparticles (LNPs) are the most common delivery approach used to formulate RNA vaccines, but existing LNP platforms have significant technical liabilities. Many LNP delivery systems must be stored between 20 C and 70 C, owing to their poor stability. This creates logistical and cost challenges related to vaccine storage and distribution. Advancements are also needed in targeting specific cells or tissues, which may mitigate undesirable toxicity and inflammation. New delivery platforms are urgently needed to provide more options and better systems for early-stage vaccine developers who are designing novel RNA-based cancer vaccines. Further innovation is expected to accelerate the future clinical translation of RNA-based vaccines to treat human cancers.