Zhai Canjia, Zheng Xiu-Jing, Song Chengcheng, Ye Xin-Shan
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Xue Yuan Rd No. 38 Beijing 100191 China
RSC Med Chem. 2021 May 19;12(7):1239-1243. doi: 10.1039/d1md00067e. eCollection 2021 Jul 21.
Globo H is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target for antitumor vaccine or cancer immunotherapies. However, most TACAs are T-cell-independent, and they cannot induce powerful immune response due to their poor immunogenicity. To address this problem, herein, several Globo H analogues with modification on the -acyl group were prepared through a preactivation-based glycosylation strategy from the non-reducing end to the reducing end. These modified Globo H derivatives were then conjugated with carrier protein CRM197 to form glycoconjugates as anticancer vaccine candidates, which were used in combination with adjuvant glycolipid C34 for immunological studies. The immunological effects of these synthetic vaccine candidates were evaluated on Balb/c mice. The results showed that the fluorine-modified -acyl Globo H conjugates can induce higher titers of IgG antibodies that can recognize the naturally occurring Globo H antigen on the surface of cancer cells and can eliminate cancer cells in the presence of a complement, indicating the potential of these synthetic glycoconjugates as anticancer vaccine candidates.
Glob H是一种肿瘤相关碳水化合物抗原（TACA），它是抗肿瘤疫苗或癌症免疫疗法的一个重要靶点。然而，大多数TACA是T细胞非依赖性的，由于其免疫原性较差，无法诱导强大的免疫反应。为了解决这个问题，本文通过基于预激活的糖基化策略，从非还原端到还原端制备了几种在酰基上有修饰的Glob H类似物。然后将这些修饰的Glob H衍生物与载体蛋白CRM197偶联形成糖缀合物作为抗癌疫苗候选物，并与佐剂糖脂C34联合用于免疫学研究。在Balb/c小鼠上评估了这些合成疫苗候选物的免疫效果。结果表明，氟修饰的酰基Glob H缀合物可诱导更高滴度的IgG抗体，该抗体能够识别癌细胞表面天然存在的Glob H抗原，并且在补体存在的情况下能够消除癌细胞，这表明这些合成糖缀合物作为抗癌疫苗候选物具有潜力。
