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

C-type lectin receptors adenovirus immunotherapy melanoma vaccine platform

Journal

Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304

Informations de publication

Date de publication:
10 Nov 2022
Historique:
received: 13 09 2022
revised: 24 10 2022
accepted: 02 11 2022
entrez: 11 11 2022
pubmed: 12 11 2022
medline: 12 11 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36359404
pii: biomedicines10112881
doi: 10.3390/biomedicines10112881
pmc: PMC9687312
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Fondation SILAB - Jean Paufique
ID : Prix de la fondation d'entreprise 2020

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Auteurs

Solène Besson (S)

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

David Laurin (D)

Immunobiology and Immunotherapy in Chronic Diseases, Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, University Grenoble Alpes, 38000 Grenoble, France.
R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, 38000 Grenoble, France.

Cyrielle Chauvière (C)

Immunobiology and Immunotherapy in Chronic Diseases, Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, University Grenoble Alpes, 38000 Grenoble, France.
R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, 38000 Grenoble, France.

Michel Thépaut (M)

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

Jean-Philippe Kleman (JP)

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

Mylène Pezet (M)

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

Olivier Manches (O)

Immunobiology and Immunotherapy in Chronic Diseases, Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, University Grenoble Alpes, 38000 Grenoble, France.
R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, 38000 Grenoble, France.

Franck Fieschi (F)

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

Caroline Aspord (C)

Immunobiology and Immunotherapy in Chronic Diseases, Institute for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, University Grenoble Alpes, 38000 Grenoble, France.
R&D Laboratory, Etablissement Français du Sang Auvergne-Rhône-Alpes, 38000 Grenoble, France.

Pascal Fender (P)

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

Classifications MeSH