title: Fully synthetic self-adjuvanting thioether-conjugated glycopeptide-lipopeptide antitumor vaccines for the induction of complement-dependent cytotoxicity against tumor cells.
abstract: 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.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Zhan-Yi
authors.initials: ZY
authors.lastname: Sun
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Horst
authors.initials: H
authors.lastname: Kunz
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000737:chemistry* / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D006020:Glycopeptides / Q000737:chemistry*; D055666:Lipopeptides / Q000737:chemistry*; D051379:Mice; D018396:Mucin-1 / Q000737:chemistry* / Q000276:immunology*; D009369:Neoplasms / Q000737:chemistry* / Q000276:immunology*; D013440:Sulfides / Q000737:chemistry*; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006020:Glycopeptides; D055666:Lipopeptides; D018396:Mucin-1; D013440:Sulfides; D014614:Vaccines, Synthetic