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A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by C-type lectin pathway-mediated tumor associated macrophages repolarizing

文献类型：期刊论文

作者Tong, Yongliang7; Chen, Runqiu4,5,6; Lu, Xinrong7; Chen, Cuiying3; Sun, Guiqin2; Yu, Xiaolu4; Lyu, Shaoxian7; Feng, Meiqing5,6; Long, Yiru4; Gong, Likun4
刊名INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
出版日期2025-04-01
卷号298页码:13
关键词Glycol-immunology Nanobody-enzyme fusion protein Sialic acid
ISSN号0141-8130
DOI10.1016/j.ijbiomac.2025.139953
英文摘要Aberrant sialylated glycosylation in the tumor microenvironment is a novel immune suppression pathway, which has garnered significant attention as a targetable glycoimmune checkpoint for cancer immunotherapy to address the dilemma of existing therapies. However, rational drug design and in-depth mechanistic studies are urgently required for tumor sialic acid to become valuable glycoimmune targets. In this study, we explored the positive correlation of PD-L1 and sialyltransferase expression in clinical colorectal cancer tissues and identified their mutual regulation effects in macrophages. Subsequently, we characterized a new sialidase with excellent properties from human oral symbiotic bacteria and then developed a novel nanobody-enzyme fusion protein, designated as Nb16-Sia, to concurrently target the PD-L1 and sialic acid. Results from syngeneic colon tumor models reveal superior efficacy of Nb16-Sia over monotherapy and combinations, which could remodel the tumor immune microenvironment. Mechanistically, Nb16-Sia, which could repolarize macrophages from the tumor-promoting M2 to anti-tumor M1 phenotype via the C-type lectin pathway, exerted its antitumor efficacy mainly by regulating tumor-associated macrophages. Our strategy of nanobody-enzyme fusion protein effectively enables the delivery of sialidase, allows the collaboration between anti-PD-L1 nanobody and sialidase in combating tumors, and holds considerable promise for further development.
WOS关键词EXPLORATION ; BLOCKADE
资助项目Gene Therapy and Clinical Studies for Fatal Conginital Disorders project[2021YFC2700800] ; National Natural Science Foundation of China[82341039] ; Postdoctoral Fellowship Program of CPSF[GZB20230797]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
语种英语
WOS记录号WOS:001406863400001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/315992]  
专题新药研究国家重点实验室
通讯作者Feng, Meiqing; Long, Yiru; Gong, Likun; Chen, Li
作者单位1.Fudan Zhangjiang Inst, Translat Glyc Res Ctr, Shanghai, Peoples R China
2.Zhejiang Chinese Med Univ, Sch Med Technol & Informat Engn, Hangzhou, Zhejiang, Peoples R China
3.Sysdiagno Nanjing Biotech Co Ltd, Dept Res & Dev, Nanjing, Jiangsu, Peoples R China
4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China
5.Fudan Univ, Sch Pharm, Dept Microbiol & Biochem Pharm, Shanghai, Peoples R China
6.Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Shanghai, Peoples R China
7.Fudan Univ, Sch Basic Med Sci, Key Lab Med Mol Virol, Dept Med Microbiol,Minist Educ & Hlth, Shanghai 200032, Peoples R China
推荐引用方式
GB/T 7714		 Tong, Yongliang,Chen, Runqiu,Lu, Xinrong,et al. A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by C-type lectin pathway-mediated tumor associated macrophages repolarizing[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2025,298:13.
APA Tong, Yongliang.,Chen, Runqiu.,Lu, Xinrong.,Chen, Cuiying.,Sun, Guiqin.,...&Chen, Li.(2025).A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by C-type lectin pathway-mediated tumor associated macrophages repolarizing.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,298,13.
MLA Tong, Yongliang,et al."A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by C-type lectin pathway-mediated tumor associated macrophages repolarizing".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 298(2025):13.

入库方式： OAI收割

来源：上海药物研究所

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