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GM3 |
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Vaxjo ID |
272 |
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Vaccine Adjuvant Name |
GM3 |
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Alternative Names |
ganglioside |
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Adjuvant VO ID |
VO_0005760
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Description |
GM3 is a ganglioside (sialylated glycosphingolipid) that binds CD169 (Siglec-1) on antigen-presenting cells (APCs), enhancing targeted uptake of liposomes for antigen/adjuvant delivery. |
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Stage of Development |
Research |
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Host Species for Testing |
Mouse |
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Components |
In this study, we incorporated TLR4 (MPLA) or TLR7/8 (3M-052) ligands in combination with inflammasome stimuli, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) or muramyl dipeptide (MDP), into GM3 liposomes. |
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Structure |
A glycosphingolipid with a ceramide backbone and one sialic acid residue linked to lactose. |
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Molecular Weight |
~1,179 g/mol |
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Storage |
Generally stored at –20°C or below in lipid film or lyophilized form. |
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Preparation |
Incorporated at 3 mol% into liposomes (phosphatidylcholine:phosphatidylglycerol:cholesterol = 3.8:1:2.5), dissolved in organic solvents, dried into lipid films, hydrated with buffer and extruded. |
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Dosage |
Liposomal dose: 200 nmol phospholipid per mouse i.v.; immunogenic peptide (OVA247–279) included at 1 mg/ml during hydration. |
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Function |
Cancer vaccination aims to activate immunity towards cancer cells and can be achieved by delivery of cancer antigens together with immune stimulatory adjuvants to antigen presenting cells (APC). APC maturation and antigen processing is a subsequent prerequisite for T cell priming and anti-tumor immunity. In order to specifically target APC, nanoparticles, such as liposomes, can be used for the delivery of antigen and adjuvant. We have previously shown that liposomal inclusion of the ganglioside GM3, an endogenous ligand for CD169, led to robust uptake by CD169-expressing APC and resulted in strong immune responses when supplemented with a soluble adjuvant. To minimize the adverse effects related to a soluble adjuvant, immune stimulatory molecules can be incorporated in liposomes to achieve targeted delivery of both antigen and adjuvant. In this study, we incorporated TLR4 (MPLA) or TLR7/8 (3M-052) ligands in combination with inflammasome stimuli, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) or muramyl dipeptide (MDP), into GM3 liposomes. Incorporation of TLR and inflammasome ligands did not interfere with the uptake of GM3 liposomes by CD169-expressing cells. GM3 liposomes containing a TLR ligand efficiently matured human and mouse dendritic cells in vitro and in vivo, while inclusion of PGPC or MDP had minor effects on maturation. Immunization with MPLA-containing GM3 liposomes containing an immunogenic synthetic long peptide stimulated CD4+ and CD8+ T cell responses, but additional incorporation of either PGPC or MDP did not translate into stronger immune responses. In conclusion, our study indicates that TLRL-containing GM3 liposomes are effective vectors to induce DC maturation and T cell priming and thus provide guidance for further selection of liposomal components to optimally stimulate anti-cancer immune responses. |
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Safety |
Well tolerated in vitro and in vivo; no significant toxicity or cell death observed. |
| References |
Nijen et al., 2022: Nijen Twilhaar MK, Czentner L, Bouma RG, Olesek K, Grabowska J, Wang AZ, Affandi AJ, Belt SC, Kalay H, van Nostrum CF, van Kooyk Y, Storm G, den Haan JMM. Incorporation of Toll-Like Receptor Ligands and Inflammasome Stimuli in GM3 Liposomes to Induce Dendritic Cell Maturation and T Cell Responses. Frontiers in immunology. 2022; 13; 842241. [PubMed: 35251040].
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