title: Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity.
abstract: Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8(+) T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy.
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Leng
authors.initials: L
authors.lastname: Jie
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Yongqi
authors.affiliation: Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Weiming
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Juqun
authors.affiliation: Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Ding
authors.initials: D
authors.lastname: Yanbing
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Xingyuan
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Mingchun
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, 225009, PR China; Department of Gastroenterology, The Second Clinical Medical College, Yangzhou University, Yangzhou, 225009, PR China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225009, PR China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, 225009, PR China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China. Electronic address: wjgong@yzu.edu.cn.
authors.forename: Gong
authors.initials: G
authors.lastname: Weijuan
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D006801:Humans; D007109:Immunity; D019409:Interleukin-15 / Q000235:genetics*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D019409:Interleukin-15; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D019444:Vaccines, DNA; D048271:Chitosan
keywords: Chitosan nanoparticle; Gene vaccine; IL-15; NKG2D; Tumor