Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy

Yuwei Li, Maoxin Fang, Haotian Yu, Xianglei Wang, Shiyao Xue, Zeze Jiang, Zixuan Huang, Shaoqin Rong, Xiaoli Wei, Zhigang Lu and Min Luo ()
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Yuwei Li: Fudan University
Maoxin Fang: Fudan University
Haotian Yu: Fudan University
Xianglei Wang: Fudan University
Shiyao Xue: Fudan University
Zeze Jiang: Fudan University
Zixuan Huang: Fudan University
Shaoqin Rong: Fudan University
Xiaoli Wei: Fudan University
Zhigang Lu: Fudan University
Min Luo: Fudan University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-59977-8

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