6533b853fe1ef96bd12ac1a4
RESEARCH PRODUCT
Fully synthetic self-adjuvanting thioether-conjugated glycopeptide-lipopeptide antitumor vaccines for the induction of complement-dependent cytotoxicity against tumor cells.
Yan-mei LiHui CaiZhi-hua HuangYufen ZhaoZhan-yi SunLei ShiHorst Kunzsubject
Epitopes T-LymphocyteAntineoplastic AgentsSulfidesCancer VaccinesCatalysisEpitopechemistry.chemical_compoundLipopeptidesMiceImmune systemAntigenAdjuvants ImmunologicNeoplasmsAnimalsAntigens Tumor-Associated CarbohydrateAmino Acid SequenceCytotoxicityVaccines SyntheticOrganic ChemistryMucin-1ToxoidGlycopeptidesLipopeptideGeneral ChemistryMolecular biologyComplement-dependent cytotoxicityGlycopeptidechemistryEpitopes B-Lymphocytedescription
Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam(3)Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation method for the synthesis of two- and three-component vaccines that contain MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam(3)CSK(4) lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund's adjuvant or in aqueous PBS buffer. The three-component vaccines that contained the Tetanus Toxoid P2 T-cell epitope peptide induced strong immune responses, even when administered just in PBS. By activation of the complement-dependent cytotoxicity (CDC) complex, the antisera induced the killing of tumor cells.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-10-17 | Chemistry (Weinheim an der Bergstrasse, Germany) |