Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy. / 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.; Chen, Xing; Clausen, Henrik; Moremen, Kelly W.; Macauley, Matthew Scott; Paulson, James C.; Wu, Peng.
In: Angewandte Chemie - International Edition, Vol. 60, No. 7, 2021, p. 3603-3610.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy
AU - Hong, Senlian
AU - Yu, Chenhua
AU - Wang, Peng
AU - Shi, Yujie
AU - Cao, Weiqian
AU - Cheng, Bo
AU - Chapla, Digantkumar G.
AU - Ma, Yuanhui
AU - Li, Jie
AU - Rodrigues, Emily
AU - Narimatsu, Yoshiki
AU - Yates, John R.
AU - Chen, Xing
AU - Clausen, Henrik
AU - Moremen, Kelly W.
AU - Macauley, Matthew Scott
AU - Paulson, James C.
AU - Wu, Peng
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - B-lymphoma
KW - CD22 ligands
KW - chemoenzymatic glycan editing
KW - E-selectin
KW - sLeX
U2 - 10.1002/anie.202005934
DO - 10.1002/anie.202005934
M3 - Journal article
C2 - 33314603
AN - SCOPUS:85097486226
VL - 60
SP - 3603
EP - 3610
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
SN - 1433-7851
IS - 7
ER -
ID: 254519438