Dendritic cell‐targeted delivery of antigens using extracellular vesicles for anti‐cancer immunotherapy

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of larg...

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Bibliographic Details
Published in:	Cell proliferation Vol. 57; no. 7; pp. e13622 - n/a
Main Authors:	Dang, Xuan T. T., Phung, Cao Dai, Lim, Claudine Ming Hui, Jayasinghe, Migara Kavishka, Ang, Jorgen, Tran, Thai, Schwarz, Herbert, Le, Minh T. N.
Format:	Journal Article
Language:	English
Published:	England John Wiley & Sons, Inc 01-07-2024 John Wiley and Sons Inc
Subjects:	Animals Antibodies Anticancer properties Antigen (tumor-associated) Antigen presentation Antigen Presentation - immunology Antigens Antigens, Neoplasm - immunology Antitumor activity Blood Cancer Cancer immunotherapy Cancer vaccines Cancer Vaccines - administration & dosage Cancer Vaccines - immunology Cell activation Cytotoxicity Dendritic cells Dendritic Cells - immunology Dendritic Cells - metabolism DNA vaccines Efficiency Erythrocytes Extracellular vesicles Extracellular Vesicles - immunology Extracellular Vesicles - metabolism Humans Immune system Immunotherapy Immunotherapy - methods Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Major histocompatibility complex Mice Mice, Inbred C57BL Nanoparticles Neoantigens Neoplasms - immunology Neoplasms - therapy Original Ovalbumin Ovalbumin - administration & dosage Ovalbumin - immunology Peptides Proteins T-Lymphocytes - immunology T-Lymphocytes - metabolism Therapeutic applications Tumors Vaccines Vesicles
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Summary:	Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large‐scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell‐derived EVs (RBCEVs) targeting splenic DEC‐205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen‐reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti‐DEC‐205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings. Red blood cell‐derived extracellular vesicles (RBCEVs) are loaded with protein antigen and are surface‐modified with DEC205‐targeting antibodies. The antigen‐loaded, DEC205‐targeting RBCEVs are taken up by dendritic cells and antigens are processed. Via DEC205‐mediated endocytosis, the antigens are digested and presented on MHC class I, which, in turn, activate CD8+ T cells. This mode of action improves T cell proliferation and activation while providing targeting effect towards secondary lymphoid organs in mice.
Bibliography:	Xuan TT Dang and Cao Dai Phung contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-7722 1365-2184 1365-2184
DOI:	10.1111/cpr.13622