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.

Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment

“…Wang et al. constructed GPC3 ‐transduced DCs and cocultured them with autologous cytokine‐induced killer cells (CIKs) . These DC‐GPC3‐CIKs exerted a strong antitumor effect against GPC3‐expressing HCC cells both in vitro and in vivo.…”

Promising new strategies for hepatocellular carcinoma

“…Dendritic cells were transduced with the GPC3 gene (DCs GPC3) and cocultured with autologous cytokine‐induced killer cells (CIKs). It was reported that DCs GPC3 CIKs significantly enhanced the cytotoxic activity against GPC3‐expressing HepG2 cells and showed significant inhibition of tumor growth in nude mice . An immunotherapy using both α‐Gal epitope‐pulsed DCs and CIK cells was evaluated.…”

DC‐CIK cells derived from ovarian cancer patient menstrual blood activate the TNFR1‐ASK1‐AIP1 pathway to kill autologous ovarian cancer stem cells

“…(4) DC‐CIK cells can kill many types of tumour cells and have the same potency against multidrug‐resistant tumour cells as they do against drug sensitive cells. (5) The tumour‐killing activity of DC‐CIK cells is not affected by immunosuppressive agents (such as cyclosporine and FK506), and DC‐CIK cells have very minimal toxicity against normal bone marrow haematopoietic precursor cells (less than 30%) …”

“…[5][6][7][8][9][10][11] CIK cells have 2 major heterogeneous cell subpopulations, CD3+/CD56+ and CD3+/CD8+. [5][6][7][8][9] Some studies have indicated that CIK cells can readily recognise cancer cells and have the advantages of both the strong anti-tumour activity of T lymphocytes and the non-MHC-restricted tumour-killing ability of NK cells. [5][6][7][8][9] Dendritic cells (DCs) are professional antigen presenting cells (APCs) that have received attention in recent years.…”