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NK cell‐mediated anti‐leukemia cytotoxicity is enhanced using a NKG2D ligand MICA and anti‐CD20 scfv chimeric protein
Author(s) -
Zou Yizhou,
Luo Weiguang,
Guo Jing,
Luo Qizhi,
Deng Mi,
Lu Zhigang,
Fang Yi,
Zhang Cheng Cheng
Publication year - 2018
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201847550
Subject(s) - nkg2d , biology , cytotoxic t cell , fusion protein , k562 cells , lymphokine activated killer cell , interleukin 21 , microbiology and biotechnology , cytotoxicity , interleukin 12 , leukemia , cancer research , recombinant dna , immunology , biochemistry , in vitro , gene
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.