可变的 PD-1 糖基化调节免疫检查点抑制剂的活性。

IF 3.3 2区 生物学 Q1 BIOLOGY
Life Science Alliance Pub Date : 2024-01-04 Print Date: 2024-03-01 DOI:10.26508/lsa.202302368
Chih-Wei Chu, Tomislav Čaval, Frederico Alisson-Silva, Akshaya Tankasala, Christina Guerrier, Gregg Czerwieniec, Heinz Läubli, Flavio Schwarz
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引用次数: 0

摘要

以免疫检查点 PD-1 为靶点的单克隆抗体为多种实体瘤带来了显著的临床疗效,但其疗效和毒性特征的差异可能与其固有的分子特性有关。在这里,我们报告了坎利珠单抗和cemiplimab通过与PD-1的岩藻糖基化聚糖相互作用而参与PD-1。利用蛋白质和细胞糖工程的组合,我们证明这两种抗体优先与天冬酰胺 N58 残基上具有核心岩藻糖的 PD-1 结合。然后,我们提供了证据,证明非小细胞肺癌患者血液中岩藻糖基化 PD-1 的浓度在疾病的不同阶段会有所不同。这项研究说明了表面受体和相关循环形式的糖谱分析如何为开发可区分糖基化变体和实现更高的选择性的分化抗体提供信息,并为实施个性化治疗方法铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Variable PD-1 glycosylation modulates the activity of immune checkpoint inhibitors.

Monoclonal antibodies targeting the immune checkpoint PD-1 have provided significant clinical benefit across a number of solid tumors, with differences in efficacy and toxicity profiles possibly related to their intrinsic molecular properties. Here, we report that camrelizumab and cemiplimab engage PD-1 through interactions with its fucosylated glycan. Using a combination of protein and cell glycoengineering, we demonstrate that the two antibodies bind preferentially to PD-1 with core fucose at the asparagine N58 residue. We then provide evidence that the concentration of fucosylated PD-1 in the blood of non-small-cell lung cancer patients varies across different stages of disease. This study illustrates how glycoprofiling of surface receptors and related circulating forms can inform the development of differentiated antibodies that discriminate glycosylation variants and achieve enhanced selectivity, and paves the way toward the implementation of personalized therapeutic approaches.

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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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