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CD22, a member of Siglec family of sialic acid binding proteins, has restricted expression on B cells. Antibody-based agents targeting CD22 or CD20 on B lymphoma and leukemia cells exhibit clinical efficacy for treating these malignancies, but also attack normal B cells leading to immune deficiency. Here, we report a chemoenzymatic glycocalyx editing strategy to introduce high-affinity and specific CD22 ligands onto NK-92MI and cytokine-induced natural killer cells to achieve tumor-specific CD22 targeting. These CD22-ligand modified cells exhibited significantly enhanced tumor cell binding and killing in vitro without harming healthy B cells. For effective lymphoma cell killing in vivo, we further functionalized CD22 ligand-modified NK-92MI cells with the E-selectin ligand sialyl Lewis X to promote trafficking to bone marrow. The dual-functionalized cells resulted in the efficient suppression of B lymphoma in a xenograft model. Our results suggest that natural killer cells modified with glycan ligands to CD22 and selectins promote both targeted killing of B lymphoma cells and improved trafficking to sites where the cancer cells reside, respectively. © 2020 Wiley-VCH GmbH.


Senlian Hong, Chenhua Yu, Peng Wang, Yujie Shi, Weiqian Cao, Bo Cheng, Digantkumar G Chapla, Yuanhui Ma, Jie Li, Emily Rodrigues, Yoshiki Narimatsu, John R Yates, Xing Chen, Henrik Clausen, Kelly W Moremen, Matthew Scott Macauley, James C Paulson, Peng Wu. Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy. Angewandte Chemie (International ed. in English). 2021 Feb 15;60(7):3603-3610

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PMID: 33314603

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