Optimization of Tannic Acid Lipid Nanoparticles for a Therapeutic mRNA Vaccine Against Melanoma

ABSTRACT Melanoma is the deadliest form of skin cancer. The FDA-approved immune checkpoint inhibitors targeting PD1 and CTLA4 and the targeted therapies against BRAF and MEK have greatly improved overall survival in metastatic melanoma. Nevertheless, many patients die from metastatic melanoma including those with inflamed tumors (i.e., tumors bearing tumor-infiltrating lymphocytes). There is therefore room to improve melanoma treatments for human patients. Here we propose the development of therapeutic mRNA vaccines against melanomas. Specifically, our proposal leverages a materials optimization approach to identify an Optimized Tannic Acid Lipid Nanoparticle Formulation that can suppress melanoma growth by delivering mRNAs encoding Melanoma-Associated Antigens into Dendritic Cell Populations. In undertaking this approach, this proposal aims to further our understanding of the mRNA delivery capabilities of Tannic Acid Lipid Nanoparticles while simultaneously laying the groundwork to advance therapeutic mRNA vaccines against melanomas toward the clinic.