Authors
Fengzhen Zhang, Yuhan Dong, Kailu Liu, Hui Hu, Huimin Chang, Jianli Zuo, Xuedan Ma, Jie Xu, Yongjun Dang, Xiaobo Wang, Hongwen Liang
Published in
Angewandte Chemie (International ed. in English). Pages e5894316. Jul 03, 2026. Epub Jul 03, 2026.
Abstract
Immune checkpoint blockades have shown great potential in cancer therapy. However, achieving efficient recruitment and activation of T cells while blocking immune suppression remains a critical challenge. Current strategies mainly focus on the blockade of the PD-1/PD-L1 axis, with limited attention to reprogramming immune functions on the tumor cell surface. Here, we report a "localized oxidation-covalent assembly" strategy that achieves precise modification of PD-L1 on the cell surface through glycan oxidation, thereby harnessing bioorthogonal reactions to induce the in situ construction of artificial topological nanostructures (ATNs), which subsequently augment T cell-mediated antitumor immunity. ATNs not only block the PD-1/PD-L1 axis to relieve immune suppression but also recruit and activate T cells through transmembrane bridging interactions, mimicking bispecific T cell engagers (BiTEs) and markedly enhancing antitumor immune responses. Mechanistic studies revealed that N-glycosylation sites are critical for probe-mediated aldehyde modification of PD-L1. We further demonstrated that the ATNs achieve spatially precise T cell recruitment and activation via PD-L1-dependent localization, enabling programmable immune regulation. Overall, this approach not only underscores the potential of glycan oxidation-driven self-assembly in immune modulation but also provides a versatile chemical biology tool for the precise reprogramming of immune checkpoint functions.
PMID:
42397842
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.
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