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

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 ® electroporation system. Nucleofection resulted in the production of IL-2 with a mean of 478.5 pg/10 6 cells (range of 107.6-1079.3 pg /10 6 cells/24 h) compared to mock transfected CIK cells (31 pg/10 6 cells) (P = 0.05). After co-culturing with DC their functional ability was assessed in vitro by 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.

Anti-CD20 antibody induces the improvement of cytokine-induced killer cell activity via the STAT and MAPK/ERK signaling pathways

“…Cytokine-induced killer (CIK) cells are major histocompatibility complex (MHC)-unrestricted cytotoxic lymphocytes that can be induced by anti-CD3 monoclonal antibody (mAb), interleukin (IL)-2, IL-1 and interferon (IFN)-γ, include CD3 + CD56 + cells and have high proliferation potential. The activity of CIK cells against tumor cells is an effective and MHC-unrestricted ( 2 , 3 ). CIK cells have the capacity to migrate toward tumor sites ( 4 , 5 ) and display antitumor activity in vivo ( 5 ).…”

Immune response, clinical outcome and safety of dendritic cell vaccine in combination with cytokine-induced killer cell therapy in cancer patients

“…Cytokine-induced killer (CIK) cells are considered to be a heterogeneous population containing the T cell marker CD3 and the natural killer (NK) cell marker CD56. As an adoptive T cell immunotherapy, CIK cells have shown significant cytotoxic activity in clinical studies (14–16). …”

Co-culture of dendritic cells and cytokine-induced killer cells effectively suppresses liver cancer stem cell growth by inhibiting pathways in the immune system

“…5 , Table 1 ). Approaches to enhance DC-CIK activity have been to modify CIK cell activity via overexpression of IL-2 with transient plasmid transfection [ 32 ] and to overexpress IL-24 in DCs via stable transfection [ 11 ]. However, in our study we focused on combined DC-CIK applications in which DCs were loaded with LCSC specific antigens, since LCSCs are reported to be the most malignant cancer cells [ 6 ].…”