title: Mouse interleukin-12/FasTI: A novel bi-functional fusion protein for cancer immuno/gene therapy.
abstract: Whereas cancer immunotherapy with cytokines in recent research was demonstrated effective in activating immune response against tumor cells, one major obstacle with the use of these cytokines is their severe side effects when delivered systemically at high doses. Another challenge is that advanced tumor cells often evade immunosurveillance of the immune system as well as of the Fas-mediated apoptosis by various mechanisms. We report the design and preliminary evaluation of the antitumor activity of a novel fusion protein-mIL-12/FasTI, consisting of mouse interleukin-12 and the transmembrane and intracellular domains of mouse Fas. The fusion construct (pmIL-12/FasTI) was transfected into mouse lung carcinoma cell line TC-1. Stable cell clones expressing the fusion protein were established as assayed by RT-PCR and immunohistochemistry. ELISA and cell proliferation analyses demonstrated that NK cells were effectively activated by the fusion protein with increased IFN-γ production and cytotoxicity. Enhanced caspase-3 activity of the clones when co-cultured with NK cells indicated that apoptosis was induced through Fas/FasL signaling pathway. The preliminary results suggest a synergized anticancer activity of the fusion protein. It may represent a promising therapeutic agent for cancer treatment.
authors.affiliation: Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Science, Southern Wesleyan University, Central, SC 29634, USA.
authors.forename: Ashlee H
authors.initials: AH
authors.lastname: Tietje
authors.affiliation: Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.
authors.forename: Yanzhang
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014162:Transfection; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D018664:Interleukin-12