Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes
Affandi, Alsya J; Grabowska, Joanna; Olesek, Katarzyna; Lopez Venegas, Miguel; Barbaria, Arnaud; Rodríguez, Ernesto; Mulder, Patrick P G; Pijffers, Helen J; Ambrosini, Martino; Kalay, Hakan; O'Toole, Tom; Zwart, Eline S; Kazemier, Geert; Nazmi, Kamran; Bikker, Floris J; Stöckl, Johannes; van den Eertwegh, Alfons J M; de Gruijl, Tanja D; Storm, Gert; van Kooyk, Yvette; den Haan, Joke M M
(2020) Proceedings of the National Academy of Sciences of the United States of America, volume 117, issue 44, pp. 27528 - 27539
(Article)
Abstract
Priming of CD8+ T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+ antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in
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vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14+ CD169+ monocytes and Axl+ CD169+ DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169+ moDCs and Axl+ CD169+ DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8+ T cells. Finally, Axl+ CD169+ DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169+ DCs to drive antitumor T cell responses.
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Keywords: Siglec-1, CD169, dendritic cells, CD8+ T cells, vaccination, Gangliosides, Humans, Immunogenicity, Vaccine, Leukocytes, Mononuclear, Liposomes, Macrophages/immunology, Neoplasms/immunology, Primary Cell Culture, Proto-Oncogene Proteins/metabolism, Receptor Protein-Tyrosine Kinases/metabolism, Sialic Acid Binding Ig-like Lectin 1/metabolism, THP-1 Cells, Vaccination/methods, Vaccines, Subunit/administration & dosage
ISSN: 0027-8424
Publisher: National Academy of Sciences
Note: Copyright © 2020 the Author(s). Published by PNAS.
(Peer reviewed)