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

Alsya J Affandi, Joanna Grabowska, Katarzyna Olesek, Miguel Lopez Venegas, Arnaud Barbaria, Ernesto Rodríguez, Patrick P G Mulder, Helen J Pijffers, Martino Ambrosini, Hakan Kalay, Tom O'Toole, Eline S Zwart, Geert Kazemier, Kamran Nazmi, Floris J Bikker, Johannes Stöckl, Alfons J M van den Eertwegh, Tanja D de Gruijl, Gert Storm, Yvette van KooykJoke M M den Haan

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)27528-27539
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number44
Publication statusPublished - 3 Nov 2020


  • 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


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