1. Selective tumor antigen vaccine delivery to human CD169 + antigen-presenting cells using ganglioside-liposomes.
- Author
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Affandi AJ, Grabowska J, Olesek K, Lopez Venegas M, Barbaria A, Rodríguez E, Mulder PPG, Pijffers HJ, Ambrosini M, Kalay H, O'Toole T, Zwart ES, Kazemier G, Nazmi K, Bikker FJ, Stöckl J, van den Eertwegh AJM, de Gruijl TD, Storm G, van Kooyk Y, and den Haan JMM
- Subjects
- Antigens, Neoplasm administration & dosage, Antigens, Neoplasm immunology, CD8-Positive T-Lymphocytes immunology, Cancer Vaccines immunology, Cross-Priming immunology, Dendritic Cells metabolism, Gangliosides, Humans, Immunogenicity, Vaccine, Leukocytes, Mononuclear, Liposomes, Macrophages metabolism, 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, Vaccines, Subunit administration & dosage, Vaccines, Subunit immunology, Axl Receptor Tyrosine Kinase, Cancer Vaccines administration & dosage, Dendritic Cells immunology, Macrophages immunology, Neoplasms therapy, Vaccination methods
- 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 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., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)- Published
- 2020
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