Synthesis and Evaluation of Glycoconjugates Comprising N-Acyl-Modified Thomsen-Friedenreich Antigens as Anticancer Vaccines
Synthesis and Evaluation of Glycoconjugates Comprising N-Acyl-Modified Thomsen-Friedenreich Antigens as Anticancer Vaccines
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包含 N-酰基修饰的 Thomsen-Friedenreich 抗原的糖复合物作为抗癌疫苗的合成和评价
DOI：
10.1002/cmdc.201600094
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发表时间：
2016
期刊：
影响因子：
3.4
通讯作者：
Ye Xin-Shan
中科院分区：
文献类型：
--
作者：
Sun Shuang;Zheng Xiu-Jing;Huo Chang-Xin;Song Chengcheng;Li Qin;Ye Xin-Shan
TF抗原是一种重要的肿瘤相关糖抗原。然而，其低免疫原性限制了其在抗癌疫苗开发中的应用。为了解决这个问题，合成了几种N-酰基修饰的TF衍生物，并将其与载体蛋白CRM 197（一种突变的白喉类毒素交叉反应物质）偶联。BALB/c小鼠的免疫学结果表明，这些修饰的TF抗原缀合物可以刺激产生与天然TF抗原交叉反应的更高滴度的IgG抗体。这些糖缀合物显示出强烈的淋巴细胞增殖反应，表明它们可以诱导细胞免疫。此外，引发的抗血清与TF阳性肿瘤细胞（4 T1）强烈反应。特别是，N-单氟乙酰基修饰的TF缀合物4-CRM 197显示出对4 T1细胞的最强的补体依赖性细胞毒性作用，这意味着这种糖缀合物作为抗癌疫苗的潜力。
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, severalN‐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, theN‐monofluoroacetyl‐modified TF conjugate4‐CRM197 showed the strongest complement‐dependent cytotoxicity effect against 4T1 cells, implying the potential of this glycoconjugate as an anticancer vaccine.