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新兴的基于聚糖的免疫反应调控策略。

Emerging glyco-based strategies to steer immune responses.

机构信息

Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Slovenia.

Technical R&D, GSK Vaccines S.r.l., Siena, Italy.

出版信息

FEBS J. 2021 Aug;288(16):4746-4772. doi: 10.1111/febs.15830. Epub 2021 May 15.

Abstract

Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell-cell communications and in the regulation of immune responses. Through the interaction with glycan-binding receptors, glycans are able to affect the activation status of antigen-presenting cells, leading either to induction of pro-inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco-chemists and glyco-immunologists to develop glycan-based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions. In this review, we highlight emerging advances in this field, and in particular, we discuss on how glycan-modified conjugates or glycoengineered cells can be employed as targeting devices to direct tumor antigens to lectin receptors on antigen-presenting cells, like dendritic cells. In addition, we address how glycan-based nanoparticles can act as delivery platforms to enhance immune responses. Finally, we discuss some of the latest developments in glycan-based therapies, including chimeric antigen receptor (CAR)-T cells to achieve targeting of tumor-associated glycan-specific epitopes, as well as the use of glycan moieties to suppress ongoing immune responses, especially in the context of autoimmunity.

摘要

糖基结构是蛋白质常见的翻译后修饰,具有多种重要的结构功能(例如在蛋白质折叠中),但也是细胞间通讯和免疫反应调节的关键参与者。通过与糖基结合受体的相互作用,糖能够影响抗原呈递细胞的激活状态,导致促炎反应的诱导或免疫抑制和免疫耐受的引发。糖的这种独特特性引起了糖化学家和糖免疫学家的兴趣,并促使他们合作开发基于糖的工具,作为治疗癌症和自身免疫性疾病等疾病的潜在治疗方法。在这篇综述中,我们强调了该领域的新进展,特别是讨论了糖基修饰的缀合物或糖工程化细胞如何作为靶向装置,将肿瘤抗原引导至抗原呈递细胞(如树突状细胞)上的凝集素受体。此外,我们还讨论了基于糖的纳米颗粒如何作为递送平台来增强免疫反应。最后,我们讨论了基于糖的治疗方法的一些最新进展,包括嵌合抗原受体 (CAR)-T 细胞以实现对肿瘤相关糖特异性表位的靶向,以及使用糖基部分来抑制正在进行的免疫反应,特别是在自身免疫的情况下。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5561/8453523/94093e983401/FEBS-288-4746-g006.jpg

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