State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and Jiangsu Key Laboratory of Drug Design and Optimization, Center of Advanced Pharmaceuticals and Biomaterials, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
Sci Adv. 2024 Mar 15;10(11):eadk2444. doi: 10.1126/sciadv.adk2444. Epub 2024 Mar 13.
Cancer vaccines show huge potential for cancer prevention and treatment. However, their efficacy remains limited due to weak immunogenicity regarding inefficient stimulation of cytotoxic T lymphocyte (CTL) responses. Inspired by the unique characteristic and biological function of high-density lipoprotein (HDL), we here develop an HDL-mimicking nanovaccine with the commendable lymph-targeted capacity to potently elicit antitumor immunity using lipid nanoparticle that is co-loaded with specific cancer cytomembrane harboring a collection of tumor-associated antigens and an immune adjuvant. The nanoparticulate impact is explored on the efficiency of lymphatic targeting and dendritic cell uptake. The optimized nanovaccine promotes the co-delivery of antigens and adjuvants to lymph nodes and maintains antigen presentation of dendritic cells, resulting in long-term immune surveillance as the elevated frequency of CTLs within lymphoid organs and tumor tissue. Immunization of nanovaccine suppresses tumor formation and growth and augments the therapeutic efficacy of checkpoint inhibitors notably on the high-stemness melanoma in the mouse models.
癌症疫苗在癌症预防和治疗方面显示出巨大的潜力。然而，由于细胞毒性 T 淋巴细胞 (CTL) 反应的刺激效率低下，其疗效仍然有限。受高密度脂蛋白 (HDL) 的独特特性和生物学功能的启发，我们在这里开发了一种 HDL 模拟纳米疫苗，该疫苗具有令人称赞的淋巴靶向能力，能够使用载有多种肿瘤相关抗原的特定癌症细胞膜和免疫佐剂的脂质纳米颗粒，有力地引发抗肿瘤免疫。研究了纳米颗粒对淋巴靶向和树突状细胞摄取效率的影响。优化后的纳米疫苗促进了抗原和佐剂向淋巴结的共递呈，并维持了树突状细胞的抗原呈递，从而导致淋巴器官和肿瘤组织中 CTL 的频率升高，实现了长期的免疫监视。纳米疫苗的免疫接种抑制了肿瘤的形成和生长，并显著增强了检查点抑制剂的治疗效果，尤其是在高干性黑色素瘤的小鼠模型中。
