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

用于黑色素瘤治疗性 mRNA 疫苗的单宁酸脂质纳米颗粒的优化

基本信息

批准号：
10727274
负责人：
Owen S Fenton
金额：
$ 22.65万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10727274
关键词：
Animals Antigens Antitumor Response BRAF gene Benchmarking CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene CTLA4 gene Cells Clinic Clinical Cytoplasm Dendritic Cells Dose FDA approved Formulation Growth Human Immune checkpoint inhibitor Immune system In Vitro MEKs Melanoma Cell Melanoma Vaccine Messenger RNA Metastatic Melanoma Mus Patients Peptides Pfizer-BioNTech COVID-19 vaccine Population Process Production Property RNA vaccine Skin Cancer Tannic Acid Therapeutic Toxic effect Training Transfection Tumor Antigens Tumor Escape Tumor Suppression Tumor-Infiltrating Lymphocytes Work cell type chemical property cost gp100 Antigen head-to-head comparison immunogenicity improved in vivo interest lipid nanoparticle lymph nodes mRNA delivery manufacturing cost melanoma melanoma-associated antigen mouse model novel programmed cell death protein 1 targeted treatment therapeutic development therapeutic vaccine treatment response tumor uptake vaccine formulation virtual

项目摘要

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.

摘要黑色素瘤是最致命的皮肤癌。FDA批准的免疫检查点抑制剂针对PD 1和CTLA 4的靶向治疗以及针对BRAF和MEK的靶向治疗总体上有了很大改善转移性黑色素瘤的生存率。然而，许多患者死于转移性黑素瘤，包括那些对于发炎的肿瘤（即，带有肿瘤浸润淋巴细胞的肿瘤）。因此，有改善的空间黑色素瘤的治疗方法。在这里，我们建议开发针对黑色素瘤的治疗性mRNA疫苗。具体来说，我们提案利用材料优化方法来确定优化的单宁酸脂质纳米颗粒通过递送编码黑色素瘤相关基因的mRNA可抑制黑色素瘤生长的制剂抗原进入树突状细胞群体。在采取这一做法时，这项建议旨在进一步加强我们的了解单宁酸脂质纳米粒的mRNA递送能力，同时铺设为将针对黑色素瘤的治疗性mRNA疫苗推向临床奠定了基础。