School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Nano Lett. 2024 Aug 21;24(33):10114-10123. doi: 10.1021/acs.nanolett.4c02196. Epub 2024 Aug 7.
Personalized cancer vaccines targeting specific neoantigens have been envisioned as one of the most promising approaches in cancer immunotherapy. However, the physicochemical variability of the identified neoantigens limits their efficacy as well as vaccine manufacturing in a uniform format. Herein, we developed a uniform nanovaccine platform based on poly(2-oxazoline)s (POx) to chemically conjugate neoantigen peptides, regardless of their physicochemical properties. This vaccine system could self-assemble into nanoparticles with uniform size (around 50 nm) and improve antigen accumulation as well as infiltration in the lymph node to increase antigen presentation. In vivo vaccination using this system conjugated with three predicted peptide neoantigen peptides from the MC38 tumor cell line induced 100% robust CD8 T cell responses and superior tumor clearance compared to free peptides. This POx-based vaccine carrier represents a generalizable approach to increase the availability and efficacy of screened neoantigen peptides for a personalized cancer vaccine.
针对特定新抗原的个体化癌症疫苗被认为是癌症免疫疗法中最有前途的方法之一。然而，所鉴定的新抗原的物理化学可变性限制了它们作为统一格式的疫苗的功效和疫苗生产。在此，我们开发了一种基于聚（2-恶唑啉）（POx）的统一纳米疫苗平台，可化学偶联新抗原肽，而不受其物理化学性质的限制。该疫苗系统可以自组装成具有均匀尺寸（约 50nm）的纳米颗粒，从而提高抗原在淋巴结中的积累和渗透，以增加抗原呈递。使用该系统偶联来自 MC38 肿瘤细胞系的三种预测的肽新抗原肽进行体内免疫接种，可诱导 100%的强 CD8 T 细胞应答，并优于游离肽的肿瘤清除率。这种基于 POx 的疫苗载体代表了一种可推广的方法，可以提高筛选出的新抗原肽的可用性和功效，用于个体化癌症疫苗。
