Biomarker-Based Metabolic Labeling for Redirected and Enhanced Immune Response
Biomarker-Based Metabolic Labeling for Redirected and Enhanced Immune Response
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DOI：
10.1021/acschembio.8b00350
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发表时间：
2018-06-01
影响因子：
4
通讯作者：
Wang, Binghe
中科院分区：
文献类型：
--
作者：
Li, Shanshan;Yu, Bingchen;Wang, Binghe
在疾病相关细胞的表面上安装抗体募集部分可以导致免疫系统选择性破坏靶标。这种方法可以成为癌症治疗和其他疾病治疗中传统化疗药物的替代策略。在这里，我们描述了一种新的策略，通过其共价和稳定的安装，选择性地标记抗体募集部分的目标，补充现有的方法，采用可逆结合。这是通过使用Ac（3）ManNAz-叶酸缀合物经由可切割接头将1，3，4-O-乙酰基-N-叠氮基乙酰甘露糖胺（Ac（3）ManNAz）选择性递送至叶酸受体过表达细胞来实现的。因此，Ac（3）ManNAz被转化为带有叠氮基的细胞表面聚糖，该叠氮基用作锚以通过与氮杂-二苯并环辛炔（DBCO）-Rha的点击反应引入L-鼠李糖（Rha）（一种半抗原）。我们在包括KB、HEK-293和MCF 7在内的几种细胞系中测试了该方法，并能够证明以下内容：1）Rha可以选择性地安装到过表达叶酸受体的细胞表面，2）安装在靶表面上的Rha可以募集抗鼠李糖（抗Rha）抗体，导致通过补体依赖性细胞毒性（CDC）和抗体依赖性细胞吞噬作用（ADCP）破坏靶细胞。
Installation of an antibody-recruiting moiety on the surface of disease-relevant cells can lead to the selective destruction of targets by the immune system. Such an approach can be an alternative strategy to traditional chemotherapeutics in cancer therapy and possibly other diseases. Herein we describe the development of a new strategy to selectively label targets with an antibody-recruiting moiety through its covalent and stable installation, complementing existing methods of employing reversible binding. This is achieved through selective delivery of 1,3,4-O-acetyl-N-azidoacetylmannosamine (Ac(3)ManNAz) to folate receptor-overexpressing cells using an Ac(3)ManNAz-folate conjugate via a cleavable linker. As such, Ac(3)ManNAz is converted to cell surface glycan bearing an azido group, which serves as an anchor to introduce L-rhamnose (Rha), a hapten, via a click reaction with aza-dibenzocyclooctyne (DBCO)-Rha. We tested this method in several cell lines including KB, HEK-293, and MCF7 and were able to demonstrate the following: 1) Rha can be selectively installed to the folate receptor overexpressing cell surface and 2) the Rha installed on the target surface can recruit anti-rhamnose (anti-Rha) antibodies, leading to the destruction of target cells via complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP).