Enhanced specific antitumor immunity of dendritic cells transduced with the glypican 3 gene and co-cultured with cytokine-induced killer cells against hepatocellular carcinoma cells.

Abstract

Dendritic cell (DC)-based cancer immunotherapy requires an immunogenic tumor-associated antigen and an effective therapeutic strategy. Glypican 3 (GPC3) is a valuable diagnostic marker and a potential therapeutic target in hepatocellular carcinoma (HCC). The present study investigated whether DCs transduced with the GPC3 gene (DCs-GPC3) and co-cultured with autologous cytokine-induced killer cells (CIKs) may induce a marked specific immune response against GPC3-expressing HCC cells in vitro and in vivo. Human DCs were transfected with a green fluorescent protein plasmid with GPC3 by nucleofection and then co-cultured with autologous CIKs. Flow cytometry was used to measure the phenotypes of DCs and CIKs. The co-cultured cells were harvested and incubated with HCC cells and the cytotoxicity of the CIKs was assessed by nonradioactive cytotoxicity assay. The anti-tumor activity of these effector cells was further evaluated using a nude mouse tumor model. The results demonstrated that DCs-GPC3 significantly promoted the autologous CIKs differentiation, as well as anti-tumor cytokine interferon-γ secretion. In addition, DCs-GPC3-CIKs significantly enhanced the cytotoxic activity against GPC3-expressing HepG2 cells, indicating a GPC3-specific marked immune response against HCC cells. The in vivo data indicated that DCs-GPC3-CIKs exhibited significant HepG2 cell-induced tumor growth inhibition in nude mice. The results of the present study provided a new insight into the design of personalizing adoptive immunotherapy for GPC3-expressing HCC cells.