Synthesis and Evaluation of Glycoconjugates Comprising N‐Acyl‐Modified Thomsen–Friedenreich Antigens as Anticancer Vaccines |
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Authors: | Shuang Sun Xiu‐Jing Zheng Chang‐Xin Huo Chengcheng Song Prof. Qin Li Prof. Xin‐Shan Ye |
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Affiliation: | State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China |
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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. |
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Keywords: | anticancer agents carbohydrates glycoconjugates TF antigens vaccines |
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