title: Treatment with a fusion protein of the extracellular domains of NKG2D to IL-15 retards colon cancer growth in mice.
abstract: Tumor-targeted cytokines are a new class of pharmaceutical anticancer agents often considered superior to the corresponding unconjugated cytokines for therapeutic purposes. We generated a new fusion protein, dsNKG2D-IL-15, in which double NKG2D extracellular domains were fused to IL-15, in Escherichia coli. This fusion protein promoted the activation, proliferation, and cytotoxicity of NK cells, and bound to NKG2D ligand-positive tumor cells. These tumor cells were also more susceptible to NK-cell attack when decorated with dsNKG2D-IL-15. The administration of mouse dsNKG2D-IL-15 protein in vivo significantly retarded the growth of transplanted colon cancers and prolonged the survival of tumor-bearing mice. Treatment with dsNKG2D-IL-15 increased the frequencies of NK and CD8 T cells in spleen and tumor tissues. The antitumor effect mediated by dsNKG2D-IL-15 was significantly decreased with in vivo depletion of NK cells or CD8 T cells. Recombinant dsNKG2D-IL-15 thus inhibited NKG2D ligand-positive tumor growth effectively by activating lymphocytes. This new biological fusion protein could potentially be used to elicit immunity in tumor-targeting treatments.
authors.affiliation: *Department of Immunology, School of Medicine †Department of Gastroenterology, the Second Clinical Medical College ‡Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Shao
authors.forename: Weiming
authors.initials: W
authors.lastname: Xiao
authors.forename: Li
authors.initials: L
authors.lastname: Qian
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ding
authors.forename: Mingchun
authors.initials: M
authors.lastname: Ji
authors.forename: Weijuan
authors.initials: W
authors.lastname: Gong
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism
chemical_list: D019409:Interleukin-15; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011993:Recombinant Fusion Proteins