6533b824fe1ef96bd1280a9b

RESEARCH PRODUCT

A Fully Synthetic Four-Component Antitumor Vaccine Consisting of a Mucin Glycopeptide Antigen Combined with Three Different T-Helper-Cell Epitopes

Markus GlaffigHorst KunzSebastian HartmannEdgar SchmittNatascha StergiouBjörn Palitzsch

subject

Molecular StructureChemistryImmunogenicityMucin-1Antigen presentationGlycopeptidesT-Lymphocytes Helper-InducerGeneral ChemistryT helper cellHuman leukocyte antigenCancer VaccinesVirologyMolecular biologyCatalysisEpitopeGlycopeptideAntigen-Antibody ReactionsEpitopesmedicine.anatomical_structureAntigenAntigens NeoplasmmedicineHumansMUC1

description

In a new concept of fully synthetic vaccines, the role of T-helper cells is emphasized. Here, a synthetic antitumor vaccine consisting of a diglycosylated tumor-associated MUC1 glycopeptide as the B-cell epitope was covalently cross-linked with three different T-helper-cell epitopes via squaric acid ligation of two linear (glyco)peptides. In mice this four-component vaccine administered without external immune-stimulating promoters elicit titers of MUC1-specific antibodies that were about eight times higher than those induced by a vaccine containing only one T-helper-cell epitope. The promising results indicate that multiple activation of different T-helper cells is useful for applications in which increased immunogenicity is required. In personalized medicine, in particular, this flexible construction of a vaccine can serve as a role model, for example, when T-helper-cell epitopes are needed that match human leukocyte antigens (HLA) in different patients.

https://doi.org/10.1002/anie.201406843