Synthesis and Evaluation of Glycoconjugates Comprising N-Acyl-Modified Thomsen-Friedenreich Antigens as Anticancer Vaccines

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• 作者：Shuang Sun ; Xiu-Jing Zheng ; Chang-Xin Huo ; Chengcheng Song ; Prof. Qin Li and Prof. Xin-Shan Ye
• 刊名：ChemMedChem
• 出版年：2016
• 出版时间：May 19, 2016
• 年：2016
• 卷：11
• 期：10
• 页码：1090-1096
• 全文大小：1006K
• ISSN：1860-7187

文摘

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.