title: A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma.
abstract: MHC class I-related chain A (MICA) is a principal immunoligand of the natural killer (NK) cell receptor NK group 2, member D (NKG2D) and plays a key role in NK cell-mediated immune recognition. Shedding of MICA from tumor cells leads to immunosuppression. To reconstitute the immunosurveilance function of NK cells, we constructed a fusion protein rG7S-MICA and explored its potential anti-tumor activity against hepatocellular carcinoma (HCC). rG7S-MICA consists of human MICA and a single-chain antibody fragment (scFv) targeting the tumor-associated antigen cluster of differentiation 24 (CD24). In vitro, rG7S-MICA engaged both NK cells and CD24(+) human HCC cells, and triggered NK cell-mediated cytolysis. Furthermore, in CD24(+) HCC-bearing nude mice, rG7S-MICA specifically targeted to the tumor tissue, where it effectively recruited NK cells and induced the release of cytokines, and showed superior anti-tumor activity. In conclusion, rG7S-MICA provides a new approach for HCC-targeting immunotherapy and has attracting potentials for clinical applications.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Fumou
authors.initials: F
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Mingying
authors.initials: M
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China. Electronic address: minwang@cpu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science & Technology, China Pharmaceutical University, Nanjing, China. Electronic address: juancpu@126.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015550:Cell Degranulation / Q000187:drug effects; D018920:Coculture Techniques; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051927:CD24 Antigen; C497889:CD24 protein, human; D016207:Cytokines; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011993:Recombinant Fusion Proteins; C000608695:rG7S-MICA protein
keywords: Antibody fusion protein; CD24; Immunosurveillance; MICA; NK cells