Synthesis and Vaccine Evaluation of the Tumor-Associated Carbohydrate Antigen RM2 from Prostate Cancer
Synthesis and Vaccine Evaluation of the Tumor-Associated Carbohydrate Antigen RM2 from Prostate Cancer
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DOI：
10.1021/ja403609x
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发表时间：
2013-07-31
影响因子：
15
通讯作者：
Wong, Chi-Huey
中科院分区：
文献类型：
--
作者：
Chuang, Hong-Yang;Ren, Chien-Tai;Wong, Chi-Huey
我们已经成功地开发了一种[1+2+3]一锅法策略来合成RM 2抗原六糖，该六糖被提议为前列腺肿瘤抗原。通过NMR分析和使用聚糖微阵列的抗体结合测定来验证合成产物的结构。此外，将合成抗原与具有不同拷贝数和佐剂组合的突变白喉毒素（DT，CRM 197）缀合以形成疫苗候选物。免疫小鼠后，我们使用聚糖微阵列来监测其免疫应答，结果表明，当一个分子的DT与平均4.7个分子的RM 2（DT-RM 4.7）结合并与糖脂C34佐剂结合时，该组合表现出最强的抗RM 2 IgG滴度。此外，诱导的小鼠抗体介导了针对前列腺癌细胞系LNCap的有效的补体依赖性细胞毒性（CDC）。
We have successfully developed a [1+2+3] one-pot strategy to synthesize the RM2 antigen hexasaccharide that was proposed to be a prostate tumor antigen. The structure of the synthetic product was verified by NMR analysis and antibody binding assay using a glycan microarray. In addition, the synthetic antigen was conjugated to a mutated diphtheria toxin (DT, CRM197) with different copy numbers and adjuvant combinations to form the vaccine candidates. After vaccination in mice, we used glycan microarrays to monitor their immune response, and the results indicated that, when one molecule of DT was incorporated with 4.7 molecules of RM2 on average (DT-RM4.7) and adjuvanted with the glycolipid C34, the combination exhibited the strongest anti-RM2 IgG titer. Moreover, the induced mouse antibodies mediated effective complement-dependent cytotoidcity (CDC) against the prostate cancer cell line LNCap.