Purpose: The interleukin-13 receptor alpha 2 (IL-13R alpha 2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. Here, we report a novel approach for targeting malignant glioma with IL-13R alpha 2- specific CTLs. Experimental Design: Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen(HLA)-A2/pIL-13R alpha 2(345-354) tetrameric complexes, anti-CD28 antibody, and CD83 molecules to cell-sized latex beads, and used to stimulate IL-13R alpha 2- specific CTLs from the peripheral blood mononuclear cells of HLA-A2(+) healthy donors. After multiple stimulations, the induced CTLs were analyzed for tetramer staining, IFN-gamma production, and CTL reactivity. Results: Tetramer staining assay showed that the induced CTLs specifically bound HLA-A2/pIL-13R alpha 2(345-354) tetramers. The CTLs specifically produced IFN-gamma in response to the HLA-A2/pIL-13R alpha 2(345-354)-aAPCs and 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), whereas 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. Conclusion: The induced 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.