复旦大学邱敏团队开发单组分LNP递送系统，用于mRNA癌症疫苗

Core Viewpoint - mRNA vaccines have shown strong clinical efficacy in preventing COVID-19, which has spurred the development of mRNA cancer vaccines as a promising strategy to elicit robust and specific anti-tumor immune responses [2][3]. Group 1: Research Development - The research team from Fudan University developed a novel single-component lipid-mRNA delivery system called OncoLRC, which efficiently targets mRNA delivery to splenic antigen-presenting cells, activating a strong anti-tumor immune response [3][11]. - Traditional lipid nanoparticles (LNPs) used in mRNA vaccines have a significant limitation of accumulating in the liver after systemic administration, prompting researchers to focus on developing splenic-targeting mRNA-LNP delivery systems [4][11]. Group 2: Mechanism and Efficacy - OncoLRC demonstrates nearly exclusive splenic targeting for mRNA delivery, outperforming traditional four-component LNP formulations, with in vivo experiments showing that mRNA is predominantly expressed in splenic antigen-presenting cells after intravenous injection [6][11]. - The OncoLRC formulation requires a lipid-to-mRNA weight ratio of 1.5:1, compared to the typical 10:1 ratio in standard LNPs, which enhances the maturation and activation of dendritic cells, leading to a strong antigen-specific immune response [8][9]. Group 3: Clinical Implications - Mechanistic studies indicate that the splenic delivery of OncoLRC is mediated primarily through macropinocytosis, enhancing the secretion of endogenous cytokines like IL-12, which further stimulates T cell activation and cytotoxic activity [9]. - In a B16F10-OVA cold tumor model, OncoLRC demonstrated significant preventive anti-tumor efficacy and exhibited a notable synergistic effect when combined with immune checkpoint blockade therapy, effectively inhibiting tumor growth [9][11].