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展示黑色素瘤肿瘤抗原的腺病毒启发的病毒样颗粒特异性靶向人类树突状细胞亚群并触发抗原特异性免疫反应。

Adenovirus-Inspired Virus-Like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses.

作者信息

Besson Solène, Laurin David, Chauvière Cyrielle, Thépaut Michel, Kleman Jean-Philippe, Pezet Mylène, Manches Olivier, Fieschi Franck, Aspord Caroline, Fender Pascal

机构信息

Institut de Biologie Structurale, CEA, CNRS, University Grenoble Alpes, UMR5075, 38042 Grenoble, France.

Immunobiology and Immunotherapy in Chronic Diseases, Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, University Grenoble Alpes, 38000 Grenoble, France.

出版信息

Biomedicines. 2022 Nov 10;10(11):2881. doi: 10.3390/biomedicines10112881.

DOI:10.3390/biomedicines10112881
PMID:36359404
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9687312/
Abstract

Virus-like particles constitute versatile vectors that can be used as vaccine platforms in many fields from infectiology and more recently to oncology. We previously designed non-infectious adenovirus-inspired 60-mer dodecahedric virus-like particles named ADDomers displaying on their surface either a short epitope or a large tumor/viral antigen. In this work, we explored for the first time the immunogenicity of ADDomers exhibiting melanoma-derived tumor antigen/epitope and their impact on the features of human dendritic cell (DC) subsets. We first demonstrated that ADDomers displaying tumor epitope/antigen elicit a strong immune-stimulating potential of human DC subsets (cDC2s, cDC1s, pDCs), which were able to internalize and cross-present tumor antigen, and subsequently cross-prime antigen-specific T-cell responses. To further limit off-target effects and enhance DC targeting, we engineered specific motifs to de-target epithelial cells and improve DCs' addressing. The improved engineered platform making it possible to display large antigen represents a tool to overcome the barrier of immune allele restriction, broadening the immune response, and paving the way to its potential utilization in humans as an off-the-shelf vaccine.

摘要

病毒样颗粒构成了多功能载体，可作为疫苗平台应用于从传染病学领域到肿瘤学等众多领域。我们之前设计了一种受非感染性腺病毒启发的60聚体十二面体病毒样颗粒，称为ADDomers，其表面展示有短表位或大的肿瘤/病毒抗原。在这项工作中，我们首次探索了展示黑色素瘤衍生肿瘤抗原/表位的ADDomers的免疫原性及其对人树突状细胞（DC）亚群特征的影响。我们首先证明，展示肿瘤表位/抗原的ADDomers能引发人DC亚群（cDC2s、cDC1s、pDCs）强大的免疫刺激潜能，这些DC亚群能够内化并交叉呈递肿瘤抗原，随后交叉启动抗原特异性T细胞反应。为了进一步限制脱靶效应并增强对DC的靶向性，我们设计了特定基序以避免靶向上皮细胞并改善对DC的靶向。这种经过改进的工程平台能够展示大抗原，是一种克服免疫等位基因限制障碍、拓宽免疫反应并为其作为现成疫苗在人类中的潜在应用铺平道路的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/58cb3d196634/biomedicines-10-02881-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/2e0205738be6/biomedicines-10-02881-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/e066171ca79a/biomedicines-10-02881-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/cbfc5296e54b/biomedicines-10-02881-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/fa297a9a9188/biomedicines-10-02881-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/06586de8000d/biomedicines-10-02881-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/66d4b8ee0078/biomedicines-10-02881-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/d27953b3229c/biomedicines-10-02881-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/65287b3cb1c0/biomedicines-10-02881-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/58cb3d196634/biomedicines-10-02881-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/2e0205738be6/biomedicines-10-02881-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/e066171ca79a/biomedicines-10-02881-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/cbfc5296e54b/biomedicines-10-02881-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/fa297a9a9188/biomedicines-10-02881-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/06586de8000d/biomedicines-10-02881-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/66d4b8ee0078/biomedicines-10-02881-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/d27953b3229c/biomedicines-10-02881-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/65287b3cb1c0/biomedicines-10-02881-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4723/9687312/58cb3d196634/biomedicines-10-02881-g009.jpg

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本文引用的文献

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