Enhanced Antitumor Immunity of a Globo H-Based Vaccine Enabled by the Combination Adjuvants of 3D-MPL and QS-21
文献类型：期刊论文
| 作者 | Ma, Wenjing4,5; Xu, Zhuojia4,5; Teng, Changcai3; Cao, Chang2; Wu, Ruixue5; Meng, Xiao4,5; Sui, Qiang1; Gao, Qi1; Zong, Chengli3; Li, Tiehai2,4,5 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2025-01-07 |
| 页码 | 11 |
| 关键词 | Carbohydrates oligosaccharide synthesis synthesis design carbohydrate-based vaccines immunological activity |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202418948 |
| 通讯作者 | Gao, Qi(Qi.gao@maxvax.cn) ; Zong, Chengli(chengli.zong@hainanu.edu.cn) ; Li, Tiehai(tiehaili@simm.ac.cn) |
| 英文摘要 | Globo H, a specific carbohydrate antigen overexpressed on various human malignancies, has attracted considerable interest as an antigenic target for anticancer vaccine development. Despite several Globo H-based carbohydrate vaccines that have been designed, efficient access to Globo H hexasaccharide antigen and development of powerful adjuvants for enhancing antitumor immunity remain challenging. Herein, we reported a streamlined chemoenzymatic approach to prepare this hexasaccharide antigen, relying on chemical synthesis of Gb5 pentasaccharide by a stereoconvergent [2+3] strategy and subsequent enzymatic alpha-fucosylation to easily install alpha 1,2-fucose residue. Separately, a modular assembly approach to efficiently synthesize 3-O-deacyl-monophosphoryl lipid A (3D-MPL) was developed by the integration of stereocontrolled glycosylation, regioselective acylation, site-specific phosphorylation, and facile global deprotection. After efficient construction of Globo H-CRM197 conjugate, we conducted systematic immunological evaluations of Globo H-CRM197 formulated with various adjuvants and adjuvant combinations, comprising saponin QS-21, synthetic 3D-MPL and alpha-galactosylceramide derivative S34. The results revealed that Globo H-CRM197 conjugate adjuvanted with QS-21 and 3D-MPL elicited robust IgG2a and IgG3 antibody responses and Th1 cellular immunity in mice. Moreover, antibodies induced by this formulation effectively bound to Globo H-positive MCF-7 cancer cells and exhibited superior complement-dependent cytotoxicity and antibody-dependent cellular phagocytosis, holding promise for further development of effective anticancer vaccines. |
| WOS关键词 | CARBOHYDRATE VACCINES ; ENZYMATIC-SYNTHESIS ; CANCER PATIENTS ; BREAST-CANCER ; ANTIGEN ; CELLS ; CONJUGATE ; IMMUNOGENICITY ; IMMUNIZATION ; MECHANISMS |
| 资助项目 | National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB1060000] ; Shanghai Municipal Science and Technology Major Project ; Hainan Provincial Natural Science Foundation of China[821CXTD1011] ; Hainan Provincial Natural Science Foundation of China[ZDYF2022SHFZ300] ; Hainan Provincial Natural Science Foundation of China[821MS028] ; [22077130] ; [22377134] ; [82073697] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001390505200001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315540]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Gao, Qi; Zong, Chengli; Li, Tiehai |
| 作者单位 | 1.Shanghai Anyikang Biotechnol Co LTD, Shanghai 200131, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 3.Hainan Univ, Sch Pharmaceut Sci, Key Lab Trop Biol Resources, Minist Educ, Haikou 570228, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Wenjing,Xu, Zhuojia,Teng, Changcai,et al. Enhanced Antitumor Immunity of a Globo H-Based Vaccine Enabled by the Combination Adjuvants of 3D-MPL and QS-21[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2025:11. |
| APA | Ma, Wenjing.,Xu, Zhuojia.,Teng, Changcai.,Cao, Chang.,Wu, Ruixue.,...&Li, Tiehai.(2025).Enhanced Antitumor Immunity of a Globo H-Based Vaccine Enabled by the Combination Adjuvants of 3D-MPL and QS-21.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,11. |
| MLA | Ma, Wenjing,et al."Enhanced Antitumor Immunity of a Globo H-Based Vaccine Enabled by the Combination Adjuvants of 3D-MPL and QS-21".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2025):11. |
入库方式： OAI收割
来源：上海药物研究所
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