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

Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27528-27539. doi: 10.1073/pnas.2006186117. Epub 2020 Oct 16.


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.

Keywords: CD169; CD8+ T cells; Siglec-1; dendritic cells; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / immunology
  • Axl Receptor Tyrosine Kinase
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Cross-Priming / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gangliosides
  • Humans
  • Immunogenicity, Vaccine
  • Leukocytes, Mononuclear
  • Liposomes
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • 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
  • Vaccines, Subunit / immunology


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Gangliosides
  • Liposomes
  • Proto-Oncogene Proteins
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1
  • Vaccines, Subunit
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human