The interleukin (IL) 13 receptor alpha 2 (IL-13R alpha 2) 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-13R alpha 2-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-13R alpha 2(345-354) 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-13R alpha 2(345-354) and HLA-A2+ glioma cells expressing IL-13R alpha 2(345-354), while HLA-A2- glioma cell lines that express IL-13R alpha 2(345-354) 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-13R alpha 2(345-354) peptide could be a potential target of specific immunotherapy for HLA-A2+ patients with malignant glioma. (C) 2007 Elsevier Ireland Ltd. All rights reserved.