Human cytokine-induced killer cells have enhanced in vitro cytolytic activity via non-viral interleukin-2 gene transfer

Genetic Vaccines and Therapy
Srinivas NagarajIngo G H Schmidt-Wolf

Abstract

Modulation of the immune system by genetically modified immunological effector cells is of potential therapeutic value in the treatment of malignancies. Interleukin-2 (IL-2) is a crucial cytokine which induces potent antitumor response. Cytokine-induced killer cells (CIK) have been described as highly efficient cytotoxic effector cells capable of lysing tumor cell targets and are capable of recognizing these cells in a non-MHC restricted fashion. Dendritic cells (DC) are the major antigen presenting cells. This study evaluated the antitumor effect of CIK cells which were non-virally transfected with IL-2 and co-cultured with pulsed and unpulsed DC. Human CIK cells generated from peripheral blood were transfected in vitro with plasmid encoding for the human IL-2. Transfection involved a combination of electrical parameters and a specific solution to deliver plasmid directly to the cell nucleus by using the Nucleofector(R) electroporation system. Nucleofection resulted in the production of IL-2 with a mean of 478.5 pg/106 cells (range of 107.6-1079.3 pg /106 cells/24 h) compared to mock transfected CIK cells (31 pg/106 cells) (P = 0.05). After co-culturing with DC their functional ability was assessed in vitro by a cytotoxicity a...Continue Reading

References

Jul 1, 1991·The Journal of Experimental Medicine·I G Schmidt-WolfI L Weissman
Jul 1, 1994·British Journal of Haematology·I G Schmidt-WolfR S Negrin
Jan 1, 1994·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·B EscudierT Hercend
Nov 1, 1996·Cancer Immunology, Immunotherapy : CII·M R Shurin
Feb 1, 1997·Annals of Hematology·G D Schmidt-WolfI G Schmidt-Wolf
Jun 1, 1997·Immunological Reviews·K A MargolinS J Forman
Dec 16, 1998·Research in Immunology·S Amigorena
Feb 15, 2002·Cancer Immunology, Immunotherapy : CII·Angela MärtenIngo H Schmidt-Wolf
Jul 30, 2003·Journal of Leukocyte Biology·Jennifer A ToomeyColin G Brooks

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Citations

Apr 17, 2012·Expert Opinion on Biological Therapy·Giulia MesianoDario Sangiolo
Apr 7, 2010·Journal of Biomedicine & Biotechnology·Yeh Ching Linn, Kam M Hui
Jul 7, 2007·European Journal of Immunology·Nada M MelhemSimon M Barratt-Boyes
Jun 4, 2005·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Seok-Gu KangJoon Ki Kang

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
density gradient centrifugation
enzyme linked immunosorbent assay
fluorescence activated cell sorter
transfection

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