Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy

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 stimu...

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Main Authors: Yuwei Li, Maoxin Fang, Haotian Yu, Xianglei Wang, Shiyao Xue, Zeze Jiang, Zixuan Huang, Shaoqin Rong, Xiaoli Wei, Zhigang Lu, Min Luo
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59977-8
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author Yuwei Li
Maoxin Fang
Haotian Yu
Xianglei Wang
Shiyao Xue
Zeze Jiang
Zixuan Huang
Shaoqin Rong
Xiaoli Wei
Zhigang Lu
Min Luo
author_facet Yuwei Li
Maoxin Fang
Haotian Yu
Xianglei Wang
Shiyao Xue
Zeze Jiang
Zixuan Huang
Shaoqin Rong
Xiaoli Wei
Zhigang Lu
Min Luo
author_sort Yuwei Li
collection DOAJ
description 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.
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spelling doaj-art-3e9abbc4702d4f52a9032fa29145db332025-08-20T03:48:18ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-59977-8Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapyYuwei Li0Maoxin Fang1Haotian Yu2Xianglei Wang3Shiyao Xue4Zeze Jiang5Zixuan Huang6Shaoqin Rong7Xiaoli Wei8Zhigang Lu9Min Luo10Institute 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 UniversityInstitute 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 UniversityInstitute 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 UniversityInstitute 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 UniversityInstitute 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 UniversityInstitute 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 UniversityInstitute 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 UniversityInstitute 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 UniversityDepartment of Pharmacology, School of Basic Medical Sciences, Fudan UniversityThe Fifth People’s Hospital of Shanghai, Institutes of Biomedical Sciences, Fudan UniversityInstitute 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 UniversityAbstract 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.https://doi.org/10.1038/s41467-025-59977-8
spellingShingle Yuwei Li
Maoxin Fang
Haotian Yu
Xianglei Wang
Shiyao Xue
Zeze Jiang
Zixuan Huang
Shaoqin Rong
Xiaoli Wei
Zhigang Lu
Min Luo
Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy
Nature Communications
title Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy
title_full Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy
title_fullStr Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy
title_full_unstemmed Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy
title_short Neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy
title_sort neoantigen enriched biomimetic nanovaccine for personalized cancer immunotherapy
url https://doi.org/10.1038/s41467-025-59977-8
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