6533b82ffe1ef96bd129506e

RESEARCH PRODUCT

A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells

Edgar SchmittNatascha StergiouSebastian HartmannHorst KunzMarkus Glaffig

subject

CD4-Positive T-Lymphocytes0301 basic medicinemedicine.medical_treatmentMannoseEnzyme-Linked Immunosorbent AssayReceptors Cell SurfaceLigands010402 general chemistryCancer Vaccines01 natural sciencesBiochemistryDivalentMice03 medical and health scienceschemistry.chemical_compoundImmune systemCancer immunotherapyDrug DiscoverymedicineAnimalsHumansLectins C-TypeGeneral Pharmacology Toxicology and PharmaceuticsMUC1Pharmacologychemistry.chemical_classificationMice Inbred BALB CbiologyChemistryMacrophagesMucin-1Organic ChemistryDendritic CellsMolecular biology0104 chemical sciencesMannose-Binding Lectins030104 developmental biologyLymphatic systemImmunoglobulin GImmunologyMCF-7 Cellsbiology.proteinMolecular MedicineLymph NodesAntibodyMannoseMannose ReceptorMannose receptorProtein Binding

description

A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose-receptor-positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non-mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4+ T cells in the local lymph organs. Comparison of di- and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose-coupled vaccine and the non-mannosylated reference vaccine induced IgG antibodies that exhibited similar binding to human breast tumor cells.

https://doi.org/10.1002/cmdc.201700646