Virus-Like Particle-Based Personalized Neoantigen Nano-Vaccine for Tumor Immunotherapy and Recurrence Prevention

作者：Shujun Zhou, Chufan Wang, Yuxiang Ning, Yunhao Wang, Yunhao Wang, Fei Xin, Lei Ren, Yanfeng Wang, Yanfeng Wang · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.5c06278 · 被引用次数：7 · 研究领域：Immunotherapy and Immune Responses、vaccines and immunoinformatics approaches、Monoclonal and Polyclonal Antibodies Research

High recurrence rates following hepatocellular carcinoma (HCC) resection remain a significant challenge, limiting the long-term prognosis of patients. Personalized antigen vaccines have emerged as a promising strategy to reduce postoperative recurrence; however, their prolonged synthesis timelines and the inherently weak immunogenicity of personalized antigens restrict their clinical applicability. To address this issue, a Plug-and-Display system was herein utilized to display “catcher” peptides, containing autocatalytic center sequences, in the major immunodominant region (MIR) of hepatitis B core protein virus-like particles (HBc VLPs), thereby engineering a universal HBc-C platform. Simultaneously, short 15-amino-acid peptide sequences containing another segment of the autocatalytic center were used to label three HCC neoantigens. The interaction between the label and the “catcher” peptides restores the functionality of the self-catalytic core, forming stable amide bonds between them and enabling the successful construction of a nanovaccine, designated HBc-MWK. In vitro assays demonstrated that HBc-MWK significantly promotes the maturation of 68.68 ± 2.51% of dendritic cells (DCs), enhances T cell activation, and induces the secretion of cytokines such as IFN-γ and GM-CSF. In xenograft tumor models, HBc-MWK markedly enhanced the intratumoral infiltration of both CD4 + and CD8 + T cells, achieving a tumor suppression rate of 97.08 ± 2.07%. In both subcutaneous and orthotopi...