Chemoenzymatic liquid-phase synthesis and immunogenic assessment of tumor-associated complex MUC1 glycopeptide variants
文献类型：期刊论文
| 作者 | Teng, Changcai7; Ma, Wenjing5,6; Liu, Jinfeng4,5,6; Hou, Juan3; Zhang, Yalong2; Meng, Xiongyan7; Xue, Yannan7; Wang, Zhen7; Wang, Jiajia4; Chen, Dexiang1 |
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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| 出版日期 | 2025-04-01 |
| 卷号 | 302页码:11 |
| 关键词 | MUC1 glycopeptide conjugate Liquid phase glycopeptide synthesis Immunological evaluations |
| ISSN号 | 0141-8130 |
| DOI | 10.1016/j.ijbiomac.2025.140525 |
| 通讯作者 | Li, Xia(lixia_kf@126.com) ; Li, Tiehai(tiehaili@simm.ac.cn) ; Zong, Chengli(chengli.zong@hainanu.edu.cn) |
| 英文摘要 | Aberrantly glycosylated Mucin 1 (MUC1) is frequently over-expressed in epithelial cancers, making it an attractive target for cancer vaccines. Over the past two decades, multiple MUC1-based vaccines have been investigated clinically, yet they have generally shown limited efficacy due to challenges such as low immunogenicity, difficulty in overcoming immune tolerance, and potential issues related to glycosylation effects and antigen presentations. To advance the understanding of MUC1 vaccines, we report an efficient chemo-enzymatic approach for the preparation of four MUC1 antigen variants with different glycoforms through liquid-phase glycopeptide synthesis. These antigen were conjugated with CRM197 to generate various glycopeptide-protein conjugate vaccines, and their immunogenicity was evaluated based on total and subtype antibody titers, binding affinity, complement-dependent cytotoxicity (CDC) activity, and antibody-dependent cellular phagocytosis (ADCP). The combination of MPL and QS21 adjuvants with STn-MUC1-CRM197 conjugate induced a potent Th1biased immune response, evidenced by elevating IgG2a titers and stronger antibody binding to MCF-7 cells. This formulation demonstrated superior CDC activity, ADCP activity and binding affinity to human breast cancer tissues in immuno-histochemical assays. The synergistic effect of specific adjuvants and glycosylated MUC1 conjugates offers a strategic avenue for MUC1 cancer vaccine development. |
| WOS关键词 | ANTITUMOR VACCINES ; IMMUNE-RESPONSE ; PROSTATE-CANCER ; IMMUNOTHERAPY ; INDUCTION ; BREAST ; MUCINS ; CELLS ; CONJUGATION ; RECOGNITION |
| 资助项目 | National Natural Science Foundation of China[22077130] ; National Natural Science Foundation of China[22377134] ; National Natural Science Foundation of China[32270977] ; National Natural Science Foundation of China[82073697] ; Strategic Priority Research Program of the Chi-nese Academy of Sciences[XDB1060000] ; Hainan Provincial Natural Science Foundation of China[821CXTD1011] ; Hainan Provincial Natural Science Foundation of China[ZDYF2022SHFZ300] ; Research Foundation of Hainan University (KYQD)[20087] ; Shanghai Municipal Science and Technology Major Project |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Polymer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001422733100001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316287]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Xia; Li, Tiehai; Zong, Chengli |
| 作者单位 | 1.Maxvax Biotechnol Co LTD, Chengdu 610200, Peoples R China 2.Binzhou Med Univ Hosp, Dept Pathol, Binzhou 256600, Peoples R China 3.Binzhou Med Univ Hosp, Clin Lab, Binzhou 256600, Peoples R China 4.Henan Univ, Sch Med, Joint Natl Lab Antibody Drug Engn, Kaifeng 475004, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, State Key Lab Chem Biol, Shanghai, Peoples R China 7.Hainan Univ, Minist Educ, Sch Pharmaceut Sci, Key Lab Trop Biol Resources, Haikou 570228, Peoples R China |
| 推荐引用方式 GB/T 7714 | Teng, Changcai,Ma, Wenjing,Liu, Jinfeng,et al. Chemoenzymatic liquid-phase synthesis and immunogenic assessment of tumor-associated complex MUC1 glycopeptide variants[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2025,302:11. |
| APA | Teng, Changcai.,Ma, Wenjing.,Liu, Jinfeng.,Hou, Juan.,Zhang, Yalong.,...&Zong, Chengli.(2025).Chemoenzymatic liquid-phase synthesis and immunogenic assessment of tumor-associated complex MUC1 glycopeptide variants.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,302,11. |
| MLA | Teng, Changcai,et al."Chemoenzymatic liquid-phase synthesis and immunogenic assessment of tumor-associated complex MUC1 glycopeptide variants".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 302(2025):11. |
入库方式： OAI收割
来源：上海药物研究所
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