Human cytokine-induced killer cells have enhanced in vitro cytolytic activity via non-viral interleukin-2 gene transfer.
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 transfectedin vitrowith 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®electroporation system. Nucleofection resulted in the production of IL-2 with a mean of 478.5 pg/106cells (range of 107.6-1079.3 pg /106cells/24 h) compared to mock transfected CIK cells (31 pg/106cells) (P= 0.05). After co-culturing with DC their functional ability was assessedin vitroby a cytotoxicity assay. On comparison with non-transfected CIK cells co-cultured with DCs (36.5 ± 5.3 %), transfected CIK cells co-cultured with DC had a significantly higher lytic activity of 58.5 ± 3.2% (P= 0.03) against Dan G cells, a human pancreatic carcinoma cell line.
Department of Internal Medicine I, General Internal Medicine Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
Srinivas
S
Nagaraj
Department of Internal Medicine I, General Internal Medicine Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
Carsten
C
Ziske
Department of Internal Medicine I, General Internal Medicine Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
Ingo Gh
IG
Schmidt-Wolf