Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines.
In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete formation of the glycan side-chains resulting from a premature sialylation, additional peptide epitopes become accessible to the immune system in mucin-type glycoproteins on tumor cells. These tumor-associated structure alterations constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens, glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor-associated sialyl-T(N), alpha2,6-sialyl-T and alpha2,3-sialyl-T antigens have been synthesized. Employing different linkers such as the allylic HYCRON or the fluoride-sensitive PTMSEL anchor, the antigenic glycopeptide structures were constructed on the solid phase utilizing pre-assembled glycosyl amino acid building blocks prepared in solution by convergent chemical or chemoenzymatic strategies. The proliferation of cytotoxic T cells has been induced applying a construct composed of a sialyl-T(N) MUC1-glycopeptide conjugated with a tetanus toxin T cell peptide epitope.
Institut für Organische Chemie, Johannes-Gutenberg-Universität Mainz, Duesbergwerg 10-14, D-55128 Mainz, Germany.
Sebastian
S
Dziadek
Horst
H
Kunz
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology; D001212:Asialoglycoproteins / Q000737:chemistry; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000276:immunology; D006801:Humans; D007114:Immunization; D009077:Mucins / Q000138:chemical synthesis / Q000276:immunology; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000628:therapy; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000276:immunology; D012794:Sialic Acids / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
D015295:Antigens, Tumor-Associated, Carbohydrate; D001212:Asialoglycoproteins; D019496:Cancer Vaccines; D006020:Glycopeptides; D009077:Mucins; D009844:Oligosaccharides; D012794:Sialic Acids; C026503:asialoglycophorin; D013912:Threonine