Li Yuwei, Fang Maoxin, Yu Haotian, Wang Xianglei, Xue Shiyao, Jiang Zeze, Huang Zixuan, Rong Shaoqin, Wei Xiaoli, Lu Zhigang, Luo Min
Institute of Pediatrics of Children's Hospital of Fudan University, the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
The Fifth People's Hospital of Shanghai, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Nat Commun. 2025 May 23;16(1):4783. doi: 10.1038/s41467-025-59977-8.
Personalized cancer vaccines elicit robust T cell immunity and anti-tumour potency, but identifying tumour-specific antigens remains challenging, severely constraining the therapeutic window. Biomimetic nanovaccines employing cancer cell membranes display inherent biocompatibility and stimulate T-cell responses against diverse tumour antigens, though tumours develop multiple mechanisms to reduce antigen presentation. Here we demonstrate a rapid and general strategy to fabricate personalized nanovaccines based on Antigen-Enriched tumor Cell Membranes (AECM) for early intervention. Interferon-γ potently stimulates antigen presentation across a broad range of cancer cell types. By coupling the generated AECM with PC7A adjuvant, a stimulator of interferon genes (STING)-activating polymer, the AECM@PC7A nanovaccine induces robust poly-neoepitopic T-cell responses even at low dosage, achieving significant tumour regression and metastasis inhibition in multiple murine cancer models. This anti-tumor response relies on MHC-I restricted antigen presentation and CD8 T-cell activation, with dendritic cells presenting AECM antigens predominantly via cross-dressing to prime T-cells. AECM@PC7A exhibits remarkable anti-tumor efficacy when compared to vaccines with diverse formulations, and demonstrates therapeutic potential in post-surgical and humanized xenograft tumor models. This proof-of-concept study provides a promising universal avenue for the rapid development of personalized cancer vaccines applicable to early intervention for a broad range of patients.
个性化癌症疫苗可引发强大的T细胞免疫和抗肿瘤效力，但识别肿瘤特异性抗原仍然具有挑战性，这严重限制了治疗窗口。采用癌细胞膜的仿生纳米疫苗具有固有的生物相容性，并能刺激针对多种肿瘤抗原的T细胞反应，不过肿瘤会产生多种机制来减少抗原呈递。在此，我们展示了一种基于富含抗原的肿瘤细胞膜（AECM）制备个性化纳米疫苗的快速通用策略，用于早期干预。干扰素-γ能有效刺激多种癌细胞类型的抗原呈递。通过将生成的AECM与PC7A佐剂（一种干扰素基因刺激因子（STING）激活聚合物）偶联，AECM@PC7A纳米疫苗即使在低剂量下也能诱导强大的多新表位T细胞反应，在多种小鼠癌症模型中实现显著的肿瘤消退和转移抑制。这种抗肿瘤反应依赖于MHC-I限制的抗原呈递和CD8 T细胞激活，树突状细胞主要通过交叉着装呈递AECM抗原以启动T细胞。与多种配方的疫苗相比，AECM@PC7A展现出显著的抗肿瘤疗效，并在术后和人源化异种移植肿瘤模型中显示出治疗潜力。这项概念验证研究为快速开发适用于广泛患者早期干预的个性化癌症疫苗提供了一条有前景的通用途径。
