Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy

被引：10
作者：
Wu, Jicheng [1 ,4 ]
Lu, Hailin [2 ]
Xu, Ximing [4 ]
Rao, Lang [1 ]
Ge, Yun [2 ,3 ]
机构：
[1] Inst Biomed Hlth Technol & Engn, Shenzhen Bay Lab, Shenzhen 518132, Peoples R China
[2] Inst Chem Biol, Shenzhen Bay Lab, Shenzhen 518132, Peoples R China
[3] Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, State Key Lab Chem Oncogen, Shenzhen 518055, Peoples R China
[4] Wuhan Univ, Renmin Hosp, Canc Ctr, Wuhan 430060, Peoples R China
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2024年 / 63卷 / 44期
基金：
中国国家自然科学基金;
关键词：
Nanobody; Glycosylation; Vesicles; Cancer Immunotherapy; HEMATOPOIETIC STEM-CELLS; HIGH-MANNOSE; ANTIBODIES; GLYCANS; CD47;
D O I：
10.1002/anie.202404889
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Immune checkpoint blockade targeting the CD47/SIRP alpha axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti-CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high-mannose glycans into the nanobody against CD47 (HM-nCD47) and subsequently displayed HM-nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM-nCD47-CVs, the nCD47 enabled the blockade of the CD47/SIRP alpha axis, and the HM enhanced recognition of mannose-binding lectin, all synergistically activating the macrophage-mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM-nCD47-CVs possessed significantly extended half-lives and increased accumulation at the tumor site, resulting in a remarkable macrophage-dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM-nCD47-CVs represent a new immunotherapeutic platform for cancer and other diseases.
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页数：11
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