Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy.
Senlian HongChenhua YuPeng WangYujie ShiWeiqian CaoBo ChengDigantkumar G ChaplaYuanhui MaJie LiEmily RodriguesYoshiki NarimatsuJohn R YatesXing ChenHenrik ClausenKelly W MoremenMatthew Scott MacauleyJames C PaulsonPeng WuPublished in: Angewandte Chemie (International ed. in English) (2020)
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.
Keyphrases
- nk cells
- induced apoptosis
- cell cycle arrest
- bone marrow
- diffuse large b cell lymphoma
- natural killer cells
- cell death
- cancer therapy
- poor prognosis
- endoplasmic reticulum stress
- single cell
- acute myeloid leukemia
- cell proliferation
- crispr cas
- cell therapy
- quantum dots
- pi k akt
- smoking cessation
- replacement therapy
- liquid chromatography