| Title | Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy |
| Authors | Hong, Senlian Yu, Chenhua Wang, Peng Shi, Yujie Cao, Weiqian Cheng, Bo Chapla, Digantkumar G. Ma, Yuanhui Li, Jie Rodrigues, Emily Narimatsu, Yoshiki Yates, John R., III Chen, Xing Clausen, Henrik Moremen, Kelly W. Macauley, Matthew Scott Paulson, James C. Wu, Peng |
| Affiliation | Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA Nankai Univ, Tianjin Med Univ Canc Inst & Hosp, Sch Med, Key Lab Breast Canc Prevent & Therapy, Tianjin 300071, Peoples R China Fudan Univ, Peoples Hosp 6, Dept Chem, Shanghai 200433, Peoples R China Fudan Univ, Peoples Hosp 6, Inst Biomed Sci, Shanghai 200433, Peoples R China Beijing Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China Univ Georgia, Complex Carbohydrate Res Ctr, 220 Riverbend Rd, Athens, GA 30602 USA Univ Alberta, Dept Chem, 11227 Saskatchewan Dr NW, Edmonton, AB T6G 2G2, Canada Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen Ctr Glyc, Copenhagen, Denmark |
| Keywords | INDUCED KILLER-CELLS SIALIC-ACID ANTIBODY BINDING BONE |
| Issue Date | Dec-2020 |
| Publisher | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION |
| Abstract | 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 nature 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. |
| URI | http://hdl.handle.net/20.500.11897/608209 |
| ISSN | 1433-7851 |
| DOI | 10.1002/anie.202005934 |
| Indexed | SCI(E) |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
