Synthesis and Vaccine Evaluation of the Tumor-Associated Carbohydrate Antigen RM2 from Prostate Cancer

被引：40

作者：

Chuang, Hong-Yang ^{[1
,2
]}

Ren, Chien-Tai ^{[1
]}

Chao, Chung-An ^{[1
]}

Wu, Chung-Yi ^{[1
]}

Shivatare, Sachin S. ^{[1
,3
,4
]}

Cheng, Ting-Jen R. ^{[1
]}

Wu, Chung-Yi ^{[1
]}

Wong, Chi-Huey ^{[1
,2
,4
]}

机构：

[1] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan

[2] Natl Taiwan Univ, Dept Chem, Taipei 106, Taiwan

[3] Acad Sinica, Taiwan Int Grad Program, Taipei 115, Taiwan

[4] Natl Taiwan Univ, Inst Biochem Sci, Taipei 106, Taiwan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2013年 / 135卷 / 30期

关键词：

ONE-POT SYNTHESIS; CROSS-REACTING MATERIAL; CELL LUNG-CANCER; GLOBO-H ANTIGEN; OLIGOSACCHARIDE SYNTHESIS; DIPHTHERIA-TOXIN; CONJUGATE VACCINE; BREAST-CANCER; IMMUNIZATION; DONORS;

D O I：

10.1021/ja403609x

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：11140 / 11150

页数：11

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