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

Title: Adenovirus-Inspired Virus-like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses
Authors: Besson, Solène; Laurin, David; Chauvière, Cyrielle; Thépaut, Michel; Kleman, Jean-Philippe; Pezet, Mylène; Manches, Olivier; Fieschi, Franck; Aspord, Caroline; Fender, Pascal
Contributors: Institut de biologie structurale (IBS - UMR 5075); Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA); Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB); Établissement Français du Sang Auvergne-Rhône-Alpes Lyon (EFS Auvergne-Rhône-Alpes - Lyon); Établissement Français du Sang La Plaine Saint-Denis (EFS)-Établissement Français du Sang La Plaine Saint-Denis (EFS)-CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA); Établissement Français du Sang La Plaine Saint-Denis (EFS); Integrated Structural Biology Grenoble (ISBG); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory Grenoble (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA); ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Source: ISSN: 2227-9059 ; Biomedicines ; https://hal.science/hal-04027183 ; Biomedicines, 2022, 10 (11), pp.2881. ⟨10.3390/biomedicines10112881⟩.
Publisher Information: CCSD; MDPI
Publication Year: 2022
Collection: Université Grenoble Alpes: HAL
Subject Terms: C-type lectin receptors; adenovirus; immunotherapy; melanoma; vaccine platform; [SDV.CAN]Life Sciences [q-bio]/Cancer; [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy; [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology; [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Description: International audience ; 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/36359404; PUBMED: 36359404; PUBMEDCENTRAL: PMC9687312
DOI: 10.3390/biomedicines10112881
Availability: https://hal.science/hal-04027183; https://hal.science/hal-04027183v1/document; https://hal.science/hal-04027183v1/file/Besson%20et%20al.%20biomedicines.pdf; https://doi.org/10.3390/biomedicines10112881
Rights: https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.BA1FDB01
Database: BASE