Oncotarget

Research Papers: Immunology:

Artificial antigen-presenting cells expressing AFP158-166 peptide and interleukin-15 activate AFP-specific cytotoxic T lymphocytes

Longhao Sun, Hao Guo, Ruoyu Jiang, Li Lu, Tong Liu, Zhixiang Zhang and Xianghui He _

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Oncotarget. 2016; 7:17579-17590. https://doi.org/10.18632/oncotarget.8198

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Abstract

Longhao Sun1, Hao Guo1, Ruoyu Jiang1, Li Lu1, Tong Liu1, Zhixiang Zhang1 and Xianghui He1

1 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China

Correspondence to:

Xianghui He, email:

Keywords: artificial antigen-presenting cells, alpha-fetoprotein, interleukin-15, cytotoxic T lymphocytes, adoptive immunotherapy, Immunology and Microbiology Section, Immune response, Immunity

Received: November 30, 2015 Accepted: March 14, 2016 Published: March 19, 2016

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 AFP158-166-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 AFP158-166 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.


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