title: Synthesis and Evaluation of Glycoconjugates Comprising N-Acyl-Modified Thomsen-Friedenreich Antigens as Anticancer Vaccines.
abstract: Thomsen-Friedenreich (TF) antigen is an important tumor-associated carbohydrate antigen. Its low immunogenicity, however, limits its application in the development of anticancer vaccines. To solve this problem, several N-acyl-modified TF derivatives were synthesized and conjugated with carrier protein CRM197 (a mutated diphtheria toxoid cross-reactive material). The immunological results in BALB/c mice demonstrated that these modified TF antigen conjugates could stimulate the production of higher titers of IgG antibodies that cross-reacted with native TF antigen. These glycoconjugates showed strong lymphocyte proliferative response, suggesting that they can induce cellular immunity. Furthermore, the elicited antisera reacted strongly with TF-positive tumor cells (4T1). In particular, the N-monofluoroacetyl-modified TF conjugate 4-CRM197 showed the strongest complement-dependent cytotoxicity effect against 4T1 cells, implying the potential of this glycoconjugate as an anticancer vaccine.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing, 100191, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing, 100191, China.
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.
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.
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: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Road No. 38, Beijing, 100191, China. liqin@bjmu.edu.cn.
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Ye
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D001426:Bacterial Proteins; D019496:Cancer Vaccines; D006001:Glycoconjugates; D007074:Immunoglobulin G; C028581:CRM197 (non-toxic variant of diphtheria toxin); C016467:Thomsen-Friedenreich antigen
keywords: TF antigens; anticancer agents; carbohydrates; glycoconjugates; vaccines