title: Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines.
abstract: Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N-acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccine V2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. xinshan@bjmu.edu.cn.
authors.forename: An
authors.initials: A
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. xinshan@bjmu.edu.cn.
authors.forename: Xiu-Jing
authors.initials: XJ
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. xinshan@bjmu.edu.cn.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. xinshan@bjmu.edu.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gui
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. xinshan@bjmu.edu.cn.
authors.forename: Chang-Xin
authors.initials: CX
authors.lastname: Huo
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing 100191, China. xinshan@bjmu.edu.cn.
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Ye
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology*; D006433:Hemocyanins / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera / Q000737:chemistry / Q000276:immunology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000737:chemistry; D009369:Neoplasms / Q000517:prevention & control
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006020:Glycopeptides; D007106:Immune Sera; D018396:Mucin-1; C055491:sialosyl-Tn antigen; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin