Increase of proliferation rate and enhancement of antitumor cytotoxicity of expanded human CD3+ CD56+ immunologic effector cells by receptor-mediated transfection with the interleukin-7 gene

Gene Therapy
S FinkeI G Schmidt-Wolf

Abstract

Cytokine-induced killer (CIK) cells have been shown to eradicate established tumors in a SCID mouse-human lymphoma model. CIK cells depend on exogenous addition of cytokines such as interleukin-2 (IL-2), interleukin-7 (IL-7) or interleukin-12 (IL-12) for proliferation. In this study, we used the adenovirus-enhanced CD3 receptor-mediated gene transfer for transfection with the IL-7 gene. An episomally replicating plasmid was used containing cDNA of the human IL-7 gene under the control of a CMV promoter for transfection of CIK cells. Biosynthesis of IL-7 was demonstrated by RT-PCR, an enzyme-linked immunosorbent assay (ELISA) and using a bioassay. Transfected cells produced IL-7 in the range between 200 and 1100 pg/10(6) cells in 24 h. IL-7 was shown to be biologically active, since transfected CIK cells showed an improved proliferation rate as compared with nontransfected cells. Expression of IL-7 altered the secretion of other cytokines by CIK cells, in particular the production of TNF alpha increased after transfection. In contrast, nontransfected CIK cells fed with IL-7 showed no increase in TNF alpha secretion. No significant differences were found in expression of surface antigens linked to the cytotoxic activity of CIK ce...Continue Reading

Citations

Aug 20, 2002·Journal of Hematotherapy & Stem Cell Research·Peter Buttgereit, Ingo G H Schmidt-Wolf
Jan 17, 2009·International Immunology·Elliott FallerPaul Macpherson
Jan 13, 2004·Genetic Vaccines and Therapy·Frank SchakowskiIngo GH Schmidt-Wolf
Sep 10, 2014·International Journal of Molecular Sciences·Frederic Carsten SchmeelIngo G H Schmidt-Wolf
Jun 6, 2008·Expert Opinion on Drug Delivery·Johannes KohlschütterMartin Trepel
Mar 27, 2012·Expert Opinion on Biological Therapy·Sharmilan ThanendrarajanIngo Schmidt-Wolf
Apr 17, 2012·Expert Opinion on Biological Therapy·Giulia MesianoDario Sangiolo
May 13, 2015·Chinese Journal of Cancer·Yelei Guo, Weidong Han
Mar 1, 2012·Biochemical and Biophysical Research Communications·K FukudaE H Chowdhury
Aug 5, 2005·Gene Therapy·L K Medina-KauweS Hamm-Alvarez
Sep 13, 2006·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Elliott M FallerPaul A MacPherson
Dec 18, 2018·Journal of Cellular Biochemistry·Solmaz ShirjangMehdi Yousefi
Jul 22, 2017·Frontiers in Immunology·Xingchun GaoWeilin Jin
Apr 22, 2014·Biomedical Reports·Qianshan TaoZhimin Zhai
May 6, 2017·Targeted Oncology·Juan J Mata-MolanesAntonio Brugarolas Masllorens

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