title: Artificial antigen-presenting cells expressing AFP(158-166) peptide and interleukin-15 activate AFP-specific cytotoxic T lymphocytes.
abstract: Professional antigen-presenting cells (APCs) are potent generators of tumor antigen-specific cytotoxic T lymphocytes (CTLs) for adoptive immunotherapy; however, generation of APCs is cumbersome, expensive, and subject to the tumor microenvironment. Artificial APCs (aAPCs) have been developed as a cost-effective alternative to APCs. We developed a cellular aAPC that efficiently generated alpha-fetoprotein (AFP)-specific CTLs. We genetically modified the human B cell lymphoma cell line BJAB with a lentiviral vector to establish an aAPC called BA15. The expression of AFP(158-166)-HLA-A*02:01 complex, CD80, CD86, and interleukin (IL)-15 in BA15 cells was assessed. The efficiency of BA15 at generating AFP-specific CTLs and the specific cytotoxicity of CTLs against AFP+ cells were also determined. BA15 cells expressed high levels of AFP(158-166) peptide, HLA-A2, CD80, CD86, and IL-15. BA15 cells also exhibited higher efficiency in generating AFP-specific CTLs than did dendritic cells. These CTLs had greater cytotoxicity against AFP+ hepatocellular carcinoma cells than did CTLs obtained from dendritic cells in vitro and in vivo. Our novel aAPC system could provide a robust platform for the generation of functional AFP-specific CTLs for adoptive immunotherapy of hepatocellular carcinoma.
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Longhao
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D056945:Hep G2 Cells; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010446:Peptide Fragments / Q000276:immunology; D011897:Random Allocation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D019409:Interleukin-15; D010446:Peptide Fragments; D000509:alpha-Fetoproteins
keywords: Immune response; Immunity; Immunology and Microbiology Section; adoptive immunotherapy; alpha-fetoprotein; artificial antigen-presenting cells; cytotoxic T lymphocytes; interleukin-15