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Redirecting Killer T Cells through Incorporation of Azido Sugars for Tethering Ligands
Author(s) -
Wang Weiling,
Zhao Zhiying,
Zhang Ziwei,
Zhang Chuanling,
Xiao Sulong,
Ye Xinshan,
Zhang Lihe,
Xia Qing,
Zhou Demin
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700340
Subject(s) - cytotoxic t cell , glycan , cytotoxicity , chemistry , chimeric antigen receptor , receptor , antigen , microbiology and biotechnology , immunotherapy , biochemistry , biology , glycoprotein , in vitro , immunology , immune system
The genetic expression of chimeric antigen receptors (CARs) on the surfaces of T cells enables the redirection of T cell specificity. To enhance the versatility of T cells as tumor‐specific killers, we developed a nongenetic approach by which azide‐containing sialic acids were metabolically incorporated into T cells to modify cellular sialyl glycans. After successful display of these moieties on the T cells, small‐molecule ligands such as RGD and folate (as proof‐of‐concept, rather than supersized antibodies) were clicked orthogonally, leading to highly selective time‐ and dose‐dependent cytotoxicity to integrin α v β 3 ‐ and folate‐receptor‐positive cells, respectively. This chemical approach provides a facile platform for rational design of tumor‐specific cytotoxic T cells for targeted immunotherapy.