Details

Autor(en) / Beteiligte

• Affandi, Alsya J.
• Grabowska, Joanna
• Olesek, Katarzyna
• Venegas, Miguel Lopez
• 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.

Titel

Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2020-11, Vol.117 (44), p.27528-27539

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2020

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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 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.