Functional characterization of interleukin-15 gene transduction into the human natural killer cell line NKL

Cytotherapy
W JiangZhigang Tian

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

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Citations

Mar 31, 2012·Frontiers of Medicine·Min ChengZhigang Tian
Apr 23, 2013·Cellular & Molecular Immunology·Min ChengZhigang Tian
Mar 19, 2011·Human Molecular Genetics·Minhtran C NgoHelen E Heslop
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
Jul 21, 2009·Journal of Internal Medicine·T Sutlu, E Alici
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
Dec 17, 2014·Cancer Letters·Lakshmi Narendra BodduluruChandra Shaker Sriram
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
Jul 25, 2019·World Journal of Gastroenterology : WJG·Yu JiangJian Zhang
Jul 20, 2010·Immunotherapy·Hollie J PegramPhillip K Darcy

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