title: 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.
authors.affiliation: Department of Clinical Laboratory Medicine, Tianjin First Central Hospital, Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin 300192, P.R. China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hernia and Abdominal Wall Surgery, Union Medicine Center, Tianjin 300121, P.R. China.
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory Medicine, Tianjin First Central Hospital, Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin 300192, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Mu
authors.affiliation: Department of Clinical Laboratory Medicine, Tianjin First Central Hospital, Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin 300192, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Union Stem and Gene Engineering Co., Tianjin 300384, P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory Medicine, Tianjin First Central Hospital, Key Laboratory for Critical Care Medicine of the Ministry of Health, Tianjin 300192, P.R. China.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D055612:Cytokine-Induced Killer Cells / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D053673:Glypicans / Q000235:genetics*; D006801:Humans; D056747:Immunomodulation; D007371:Interferon-gamma / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D010641:Phenotype; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans; D007371:Interferon-gamma