Jiang Xiaobing, Lu Xiaoling, Liu Ruen, Zhang Fangcheng, Zhao Hongyang
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Clin Cancer Res. 2007 Dec 15;13(24):7329-34. doi: 10.1158/1078-0432.CCR-07-1025.
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.
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.
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.
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.
白细胞介素-13受体α2（IL-13Rα2）是一种胶质瘤限制性细胞表面表位，在中枢神经系统其他部位未检测到。在此，我们报告一种用IL-13Rα2特异性细胞毒性T淋巴细胞（CTL）靶向恶性胶质瘤的新方法。
通过将人白细胞抗原（HLA）-A2/pIL-13Rα2（345-354）四聚体复合物、抗CD28抗体和CD83分子包被到细胞大小的乳胶珠上制备人工抗原呈递细胞（aAPC），并用于刺激来自HLA-A2+健康供体外周血单个核细胞的IL-13Rα2特异性CTL。多次刺激后，分析诱导的CTL的四聚体染色、γ干扰素产生和CTL反应性。
四聚体染色分析表明，诱导的CTL特异性结合HLA-A2/pIL-13Rα2（345-354）四聚体。CTL对HLA-A2/pIL-13Rα2（345-354）-aAPC特异性产生γ干扰素，并对用肽pIL-13Rα2（345-354）脉冲处理的T2细胞和表达IL-13Rα2（345-354）的HLA-A2+胶质瘤细胞表现出特异性裂解，而表达IL-13Rα2（345-354）的HLA-A2（-）胶质瘤细胞系不能被CTL识别。肽特异性活性被抗HLA I类单克隆抗体抑制。
诱导的针对IL-13Rα2（345-354）肽的CTL可能是HLA-A2+恶性胶质瘤患者特异性免疫治疗的潜在靶点。
