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

• Published in: Biomedicines Vol. 10; no. 11; p. 2881
• Main Authors: Besson, Solène, Laurin, David, Chauvière, Cyrielle, Thépaut, Michel, Kleman, Jean-Philippe, Pezet, Mylène, Manches, Olivier, Fieschi, Franck, Aspord, Caroline, Fender, Pascal
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.11.2022; MDPI
• Subjects: adenovirus; Adenoviruses; Antigens; C-type lectin receptors; Cancer; Cloning; Cytotoxicity; Dendritic cells; Dermatology; Epithelial cells; Epitopes; Health aspects; Human health and pathology; Immune system; Immunogenicity; Immunology; Immunotherapy; Life Sciences; Lymphocytes; Lymphocytes T; Melanoma; Peptides; Proteins; Severe acute respiratory syndrome coronavirus 2; Sucrose; Tumors; vaccine platform; Vaccines; Vaccinology; Virus-like particles; Viruses; France; Paris France; vaccine platform; melanoma; C-type lectin receptors; adenovirus; immunotherapy
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10112881

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.