Abstract
Genetic modification of natural killer (NK) cells is a potential approach to gene-based immunotherapy of cancer. We created human interleukin-15 (hIL-15) gene-modified NKL cells and investigated their functional characterization in vitro. A recombinant vector (pcDNA3-IL15) or control vector (pcDNA3) was transferred into NKL cells by an electroporation method. Standard reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry and MTT methods were performed for NK cell proliferation, apoptosis, cytotoxicity assays and gene expression tests. Compared with parental NKL cells, hIL-15 gene modification promoted NK cell proliferation at low doses of IL-2 and inhibited cell apoptosis, which was associated with the up-regulation of anti-apoptosis genes Bcl-2, Bcl-xl and Mcl-1 as well as the down-regulation of apoptosis genes Bim and Noxa. Moreover, the anti-tumor activity of hIL-15 gene-transduced NKL cells against human hepatoma cancer cell line HepG2, H7402 and PLC/PRF-5 cells was enhanced, at least partly, through increasing expression of cytotoxicity-associated genes, including interferon (IFN)-gamma, perforin and FasL. The hIL-15 genetic modification could improve the proliferation, anti-apoptosis and natural cytotox...Continue Reading
References
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J F Bazan
Oct 1, 1994·The Journal of Experimental Medicine·W E CarsonM A Caligiuri
May 13, 1994·Science·K H GrabsteinM Ahdieh
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·J D BurtonT A Waldmann
Jan 1, 1996·Annual Review of Immunology·A MorettaL Moretta
May 23, 1998·Annual Review of Immunology·L L Lanier
Jun 8, 1999·Annual Review of Immunology·T A Waldmann, Y Tagaya
Jun 8, 1999·Annual Review of Immunology·C A BironT P Salazar-Mather
Jun 12, 1999·Human Gene Therapy·Y K TamH G Klingemann
Jan 3, 2001·Blood·T A Fehniger, M A Caligiuri
Mar 3, 2001·Current Opinion in Immunology·M J Soloski
Mar 22, 2002·Nature Reviews. Immunology·A Cerwenka, L L Lanier
Oct 24, 2002·Blood·Megan A CooperMichael A Caligiuri
Nov 20, 2002·Immunogenetics·Makoto YawataPeter Parham
Feb 15, 2003·Blood·Thomas RansonJames P Di Santo
Jan 23, 2004·Journal of Immunological Methods·Kerima MaashoFrancisco Borrego
Feb 3, 2004·Journal of Cellular and Molecular Medicine·R BiassoniN Dimasi
Apr 30, 2004·Cell Stress & Chaperones·Catharina GrossGabriele Multhoff
Nov 3, 2004·Vaccine·John R Yannelli, Joanne M Wroblewski
Nov 24, 2004·Investigative Ophthalmology & Visual Science·Yu-Guang HeJerry Y Niederkorn
Feb 1, 2005·Journal of Immunological Methods·Eric M Grund, Robin C Muise-Helmericks
Mar 11, 2005·Expert Opinion on Biological Therapy·Sally Arai, Hans-G Klingemann
Mar 16, 2005·Current Opinion in Immunology·Loredana RuggeriAndrea Velardi
Jun 28, 2005·Veterinary Immunology and Immunopathology·Changyun XiongC Wayne Smith
Aug 18, 2006·Seminars in Cancer Biology·Garnet Suck
Jul 10, 2007·Nature Immunology·Nicholas D HuntingtonAndreas Strasser
Feb 19, 2008·Cytokine·Cai ZhangZhigang Tian
Citations
Feb 9, 2012·Cancer Immunology, Immunotherapy : CII·Christiane SahmWinfried S Wels
Mar 31, 2012·Frontiers of Medicine·Min ChengZhigang Tian
Apr 23, 2013·Cellular & Molecular Immunology·Min ChengZhigang Tian
Jun 14, 2013·Gene Therapy·W JiangJ Zhang
Mar 19, 2011·Human Molecular Genetics·Minhtran C NgoHelen E Heslop
May 7, 2013·Transplantation·Fei WangJian Zhang
Aug 30, 2013·Virology Journal·Haotian YuJian Zhang
Oct 15, 2011·Immunotherapy·Anshu Malhotra, Anil Shanker
Jul 11, 2014·Journal of Immunology Research·Dong-Sup ChungYong-Kil Hong
Feb 18, 2016·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Letícia BaggioDean Anthony Lee
Jun 28, 2011·Experimental Hematology·Garnet SuckMickey B C Koh
Dec 10, 2015·Frontiers in Immunology·Carin I M DahlbergEvren Alici
Jul 21, 2009·Journal of Internal Medicine·T Sutlu, E Alici
Feb 24, 2011·Journal of Cellular and Molecular Medicine·Alena DabrazhynetskayaVictor Levitsky
Jun 16, 2015·Acta Pharmacologica Sinica·Cheng SunZhi-gang Tian
Jun 27, 2015·Frontiers in Immunology·Mattias Carlsten, Richard W Childs
Jun 20, 2015·Frontiers in Immunology·Okjae LimEui-Cheol Shin
Apr 12, 2014·Immunobiology·Wen JiangJian Zhang
Dec 17, 2014·Cancer Letters·Lakshmi Narendra BodduluruChandra Shaker Sriram
May 22, 2008·PloS One·Massimo GiulianiBruno Azzarone
Aug 5, 2016·Journal of Immunotherapy·Diana ResetcaJeffrey A Medin
May 9, 2018·Journal of Cancer Research and Clinical Oncology·Wen JiangJian Zhang
May 18, 2020·Stem Cells Translational Medicine·May Sabry, Mark W Lowdell
Sep 30, 2020·Journal of Leukocyte Biology·Raynier DevillierDaniel Olive
Jul 25, 2019·World Journal of Gastroenterology : WJG·Yu JiangJian Zhang
Nov 23, 2017·Disease Markers·Tao ZhangZhihai Peng
Sep 15, 2018·Cancer Cell International·Faezeh HosseinzadehSadegh Shirian
Oct 12, 2018·Journal of Immunology Research·Sandro Matosevic
Jul 20, 2010·Immunotherapy·Hollie J PegramPhillip K Darcy