Chemical remodeling cell surface glycans for immunotargeting of tumor cells

Recruitment of human endogenous antibodies to target and eliminate tumor cells is a promising therapeutic strategy in the biomedical field. Current antibody-recruiting molecules are typically bi-functional agents that utilize cell-surface receptor binding property for targeting. This approach has in...

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Bibliographic Details
Published in:Carbohydrate research 2017-11, Vol.452, p.25-34
Main Authors: Li, Xuexia, Xu, Xiaoyan, Rao, Xiongjian, Tian, Yinping, Yi, Wen
Format: Article
Language:English
Subjects:
A549 Cells
Animals
Antibodies - immunology
Antibodies, Monoclonal - immunology
Cell Line, Tumor
Epitopes - immunology
HeLa Cells
Humans
Liposomes
Metabolic Engineering
Mice
Mice, Inbred BALB C
Polysaccharides - immunology
Rhamnose - immunology
Xenograft Model Antitumor Assays
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Summary:Recruitment of human endogenous antibodies to target and eliminate tumor cells is a promising therapeutic strategy in the biomedical field. Current antibody-recruiting molecules are typically bi-functional agents that utilize cell-surface receptor binding property for targeting. This approach has intrinsic limitations due to the heterogeneity of tumor cells and the limited number of receptors on the cell surface. Here we report a targeting strategy based on remodeling of cell surface glycans through metabolic engineering and bioorthogonal chemical ligation. In vitro cultured tumor cells and in vivo xenograft tumors were actively remodeled with rhamnose carbohydrate epitopes, which were capable of recruiting endogenous anti-rhamnose antibodies and activating complement-mediated cell cytotoxicity. This study highlights the therapeutic potential for modulating endogenous immune response through cell-surface glycan engineering. [Display omitted] •Cell surface glycans are chemically remodeled with rhamnose epitopes.•Cell surface remodeled with rhamnose activates complement-mediated cytotoxicity.•Cell surface glycan engineering can potentially modulate immune response.
ISSN:0008-6215
1873-426X
DOI:10.1016/j.carres.2017.10.003