Abstract
NK cells are important innate cytotoxic lymphocytes that have potential in treatment of leukemia. Engagement of NKG2D receptor on NK cells enhances the target cytotoxicity. Here, we produced a fusion protein consisting of the extracellular domain of the NKG2D ligand MICA and the anti-CD20 single-chain variable fragment (scfv). This recombinant protein is capable of binding both NK cells and CD20 + tumor cells. Using a human NKG2D reporter cell system we developed, we showed that this fusion protein could decorate CD20 + tumor cells with MICA extracellular domain and activate NK through NKG2D. We further demonstrated that this protein could specifically induce the ability of a NK cell line (NKL) and primary NK cells to lyse CD20 + leukemia cells. Moreover, we found that downregulation of surface HLA class I expression in the target cells improved NKL-mediated killing. Our results demonstrated that this recombinant protein specifically lyses leukemia cells by NK cells, which may lead to development of a novel strategy for treating leukemia and other tumors.
Original language | English (US) |
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Pages (from-to) | 1750-1763 |
Number of pages | 14 |
Journal | European Journal of Immunology |
Volume | 48 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2018 |
Keywords
- CD20
- Chimeric protein
- Cytotoxicity
- MICA
- NKG2D
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology