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

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 靶向PD1和CTLA4以及针对BRAF和MEK的靶向治疗总体上有了很大改善 转移性黑色素瘤的存活率。然而，许多患者死于转移性黑色素瘤，包括 炎性肿瘤(即含有肿瘤浸润性淋巴细胞的肿瘤)。因此，还有改进的余地。 人类患者的黑色素瘤治疗。 在此，我们建议开发针对黑色素瘤的治疗性mRNA疫苗。具体地说，我们的 该方案利用材料优化方法来确定优化的单宁酸脂纳米颗粒 通过传递编码黑色素瘤相关基因的mRNAs抑制黑色素瘤生长的制剂 抗原进入树突状细胞群体。通过采用这种方法，这项建议的目的是进一步推动我们的 单宁酸脂纳米粒同时产蛋时信使核糖核酸传递能力的研究 为将黑色素瘤治疗性基因疫苗推向临床奠定基础。

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.