NK cell-mediated anti-leukemia cytotoxicity is enhanced using a NKG2D ligand MICA and anti-CD20 scfv chimeric protein

Yizhou Zou, Weiguang Luo, Jing Guo, Qizhi Luo, Mi Deng Ph.D., Zhigang Lu, Yi Fang, Chengcheng Zhang

Research output: Contribution to journalArticle

1 Scopus citations


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 languageEnglish (US)
Pages (from-to)1750-1763
Number of pages14
JournalEuropean Journal of Immunology
Issue number10
StatePublished - Oct 1 2018



  • CD20
  • Chimeric protein
  • Cytotoxicity
  • MICA
  • NKG2D

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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