Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager

Yang, Zhuo; Hou, Yingqin; Grande, Geramie; Cho, Jong Hyun; Wang, Chao; Shi, Yujie; Zak, Jaroslav; Wan, Yue; Qin, Ke; Liu, Dongfang; Teijaro, John R.; Lerner, Richard A.; Wu, Peng

doi:10.1038/s41551-024-01202-w

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2024

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Cited by 2 publications

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Glycoengineering in antigen-specific immunotherapies

Li,

Chen,

Gao

et al. 2024

Current Opinion in Chemical Biology

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Glycoengineering in antigen-specific immunotherapies

Li,

Chen,

Gao

et al. 2024

Current Opinion in Chemical Biology

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A Unified Atlas of T cell Glycophysiology

Izzati,

Choksi,

Giuliana

et al. 2024

Preprint

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SUMMARYGlycans are emerging as important regulators of T cell function but remain poorly characterized across the functionally distinct populations that existin vivo. Here, we couple single-cell analysis technologies with soluble lectins and chemical probes to interrogate glycosylation patterns on major T cell populations across multiple mouse and human tissues. Our analysis focused on terminal glycan epitopes with immunomodulatory functions, including sialoglycan ligands for Siglecs. We demonstrate that glycosylation patterns are diverse across the resting murine T cell repertoire and dynamically remodelled in response to antigen-specific stimulation. Surprisingly, we find that human T cell populations do not share the same glycoprofiles or glycan remodelling dynamics as their murine counterparts. We show that these differences can be explained by divergent regulation of glycan biosynthesis pathways between the species. These results highlight fundamental glycophysiological differences between mouse and human T cells and reveal features that are critical to consider for glycan-targeted therapies.

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Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager

Cited by 2 publications

References 46 publications

Glycoengineering in antigen-specific immunotherapies

Glycoengineering in antigen-specific immunotherapies

A Unified Atlas of T cell Glycophysiology

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