title: A totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for cancer therapy.
abstract: In the development of vaccines for epithelial tumors, the key targets are MUC1 proteins, which have a variable number of tandem repeats (VNTR) bearing tumor-associated carbohydrate antigens (TACAs), such as Tn and STn. A major obstacle in vaccine development is the low immunogenicity of the short MUC1 peptide. To overcome this obstacle, we designed, synthesized, and evaluated several totally synthetic self-adjuvanting vaccine candidates with self-assembly domains. These vaccine candidates aggregated into fibrils and displayed multivalent B-cell epitopes under mild conditions. Glycosylation of Tn antigen on the Thr residue of PDTRP sequence in MUC1 VNTR led to effective immune response. These vaccines elicited a high level antibody response without any adjuvant and induced antibodies that recognized human breast tumor cells. These vaccines appeared to act through a T-cell independent pathway and were associated with the activation of cytotoxic T cells. These fully synthetic, molecularly defined vaccine candidates had several features that hold promise for anticancer therapy.
authors.affiliation: Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Ma
authors.forename: Zhan-Yi
authors.initials: ZY
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Chen
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D019496:Cancer Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry* / Q000235:genetics; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D019496:Cancer Vaccines; D018396:Mucin-1; D010446:Peptide Fragments