Generation of allo-restricted cytotoxic T lymphocytes against malignant glioma by artificial antigen-presenting cells

• Published in: Cancer letters Vol. 256; no. 1; pp. 128 - 135
• Main Authors: Lu, Xiao-ling, Jiang, Xiao-bing, Liu, Ru-en, Zhang, Fang-cheng, Zhao, Hong-yang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 18.10.2007; Elsevier Limited
• Subjects: Allo-restricted cytotoxic T lymphocytes (allo-restricted CTLs); Antibiotics; Antigen-Presenting Cells - immunology; Artificial antigen-presenting cells (aAPCs); Cell culture; Cytotoxicity; Enzyme-Linked Immunosorbent Assay; Epitopes - chemistry; Epitopes - immunology; Glioma - immunology; Hematology, Oncology and Palliative Medicine; HLA-A2 Antigen - immunology; Humans; Interleukin 13 receptor α2 (IL-13Rα2); Interleukin-13 Receptor alpha2 Subunit - immunology; Lymphocytes; Malignant glioma; Mortality; Patients; Peptide Fragments - immunology; Peptide Fragments - pharmacology; Peptides; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured - immunology; Tumors; Malignant glioma; Artificial antigen-presenting cells (aAPCs); Allo-restricted cytotoxic T lymphocytes (allo-restricted CTLs); Interleukin 13 receptor α2 (IL-13Rα2)
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2007.07.015

Abstract The interleukin (IL) 13 receptor α2 (IL-13Rα2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. This study reported a novel approach for targeting malignant glioma with IL-13Rα2-specific allo-restricted cytotoxic T cells (CTLs) induced from the peripheral blood lymphocytes (PBLs) of HLA-A2-negative healthy donors by multiple stimulations with artificial antigen-presenting cells (aAPCs) made by coating HLA-A2/pIL-13Rα2345–354 tetrameric complexes, anti-CD28 antibody and CD83 molecules to cell-sized latex beads. The induced allo-restricted CTLs exhibited specific lysis against T2 cells pulsed with the peptide pIL-13Rα2345–354 and HLA-A2+ glioma cells expressing IL-13Rα2345–354 , while HLA-A2− glioma cell lines that express IL-13Rα2345–354 could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-HLA class I monoclonal antibody. These results suggested the induced allo-restricted CTLs specific for IL-13Rα2345–354 peptide could be a potential target of specific immunotherapy for HLA-A2+ patients with malignant glioma.