Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
J Am Chem Soc. 2013 Jul 31;135(30):11140-50. doi: 10.1021/ja403609x. Epub 2013 Jul 17.
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 cytotoxicity (CDC) against the prostate cancer cell line LNCap.
我们成功开发了一种[1+2+3]一锅法策略，用于合成 RM2 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试验验证了合成产物的结构。此外，将合成抗原与不同拷贝数和佐剂组合的突变白喉毒素（DT，CRM197）缀合形成疫苗候选物。在小鼠中接种疫苗后，我们使用聚糖微阵列监测它们的免疫反应，结果表明，当平均每个 DT 分子与 4.7 个 RM2 分子结合（DT-RM4.7）并与糖脂 C34 佐剂时，该组合表现出最强的抗 RM2 IgG 效价。此外，诱导的小鼠抗体介导了对前列腺癌细胞系 LNCap 的有效补体依赖性细胞毒性（CDC）。
