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

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Principal Investigator: Owen S Fenton
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2024
Award: $226,293
Funding agency: National Institute of Biomedical Imaging and Bioengineering

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.

Terms: <Animals><Antigens><Antitumor Response><B-raf-1><BNT 162b2><BNT162b2><BRAF><BRAF gene><Benchmarking><Best Practice Analysis><CD152><CD152 Antigen><CD152 Gene><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><CTLA 4><CTLA-4 Gene><CTLA4><CTLA4 gene><CTLA4-TM><Cell Body><Cells><Checkpoint inhibitor><Clinic><Clinical><Cytoplasm><Cytotoxic T-Lymphocyte Protein 4><Cytotoxic T-Lymphocyte-Associated Antigen 4><Cytotoxic T-Lymphocyte-Associated Protein 4><Cytotoxic T-Lymphocyte-Associated Serine Esterase-4><Dendritic Cells><Dose><FDA approved><Formulation><Generalized Growth><Growth><Human><Immune checkpoint inhibitor><Immune system><In Vitro><LYT3><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic nodes><MEKs><Malignant Melanoma><Malignant Skin Neoplasm><Melanoma><Melanoma Cell><Melanoma Metastasis><Melanoma Vaccine><Messenger RNA><Metastatic Melanoma><Mice><Mice Mammals><Modern Man><Molecular Tumor Suppression><Murine><Mus><PD 1><PD-1><PD1><Patients><Peptides><Pfizer covid19 vaccine><Pfizer-BioNTech COVID-19 vaccine><Pfizer-BioNTech coronavirus disease 2019 vaccine><Pfizer/BioNTech vaccine><Population><Process><Production><Property><RAFB1><RNA vaccine><RNA-based vaccine><Skin Cancer><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Tannic Acid><Tannins><Therapeutic><Tissue Growth><Toxic effect><Toxicities><Training><Transfection><Tumor Antigens><Tumor Escape><Tumor Immune Escape><Tumor Suppression><Tumor-Associated Antigen><Tumor-Infiltrating Lymphocytes><Veiled Cells><Work><anti-tumor response><benchmark><cancer antigens><cancer evasion><cancer immune escape><cancer immune evasion><cell type><chemical property><cost><cytotoxic T-lymphocyte antigen 4><deliver mRNA><deliver messenger RNA><delivery system for mRNA><fabrication cost><glycoprotein 100><gp 100><gp100 Antigen><head-to-head analysis><head-to-head comparison><immune check point inhibitor><immunogen><immunogenicity><improved><in vivo><interest><lipid based nanoparticle><lipid nanoparticle><lymph gland><lymph nodes><lymphnodes><mRNA><mRNA delivery><mRNA vaccine><mRNA-based vaccine><malignant skin tumor><manufacturing cost><melanoma-associated antigen><messenger RNA delivery><mouse model><murine model><novel><ontogeny><programmed cell death 1><programmed cell death protein 1><programmed death 1><response to therapy><response to treatment><sle2><systemic lupus erythematosus susceptibility 2><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic agent development><therapeutic development><therapeutic response><therapeutic vaccine><therapy response><treatment response><treatment responsiveness><treatment vaccines><tumor><tumor evasion><tumor immune evasion><tumor-specific antigen><uptake><v-raf Murine Sarcoma Viral Oncogene Homolog B1><vaccine for the treatment><vaccine for treatment><vaccine formulation><virtual>