Journal
JOURNAL OF CONTROLLED RELEASE
Volume 331, Issue -, Pages 309-320Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2021.01.029
Keywords
Liposomes; CD169; Siglec-1; Macrophage; Dendritic cell; T cell response
Funding
- Dutch Cancer Society [VU2016-10449]
- NWO ZonMW TOP [91218024]
- Phospholipid Research Center [JDH-2020-082/1-1]
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In this study, liposomes containing GM3 were shown to efficiently target CD169(+) macrophages, inducing specific immune responses including antigen-specific CD8(+) and CD4(+) T cell as well as B cell responses. Administration of GM3 liposomes containing ovalbumin resulted in delayed tumor growth and improved survival in B16-OVA tumor bearing mice. The study also highlighted the essential role of CD169(+) macrophages and cDC1s in inducing CD8(+) T cell immunity through liposomal vaccination.
Cancer vaccines aim to efficiently prime cytotoxic CD8(+) T cell responses which can be achieved by vaccine targeting to dendritic cells. CD169(+) macrophages have been shown to transfer antigen to dendritic cells and could act as an alternative target for cancer vaccines. Here, we evaluated liposomes containing the CD169/ Siglec-1 binding ligand, ganglioside GM3, and the non-binding ligand, ganglioside GM1, for their capacity to target antigens to CD169(+) macrophages and to induce immune responses. CD169(+) macrophages demonstrated specific uptake of GM3 liposomes in vitro and in vivo that was dependent on a functional CD169 receptor. Robust antigen-specific CD8(+) and CD4(+) T and B cell responses were observed upon intravenous administration of GM3 liposomes containing the model antigen ovalbumin in the presence of adjuvant. Immunization of B16-OVA tumor bearing mice with all liposomes resulted in delayed tumor growth and improved survival. The absence of CD169(+) macrophages, functional CD169 molecules, and cross-presenting Batf3-dependent dendritic cells (cDC1s) significantly impaired CD8(+) T cell responses, while B cell responses were less affected. In conclusion, we demonstrate that inclusion of GM3 in liposomes enhance immune responses and that splenic CD169(+) macrophages and cDC1s are required for induction of CD8(+) T cell immunity after liposomal vaccination.
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