This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jiang, X. Articles by Zhao, H. Search for Related Content PubMed PubMed Citation Articles by Jiang, X. Articles by Zhao, H.

HLA Tetramer–Based Artificial Antigen-Presenting Cells Efficiently Stimulate CTLs Specific for Malignant Glioma

Authors' Affiliations: ¹ Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; ² Department of Immunology, Shanghai Medical College, Fudan University, Shanghai, China; and ³ Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China

Requests for reprints: Xiaobing Jiang, Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Phone: 86-27-8535-1616; E-mail: jxb917{at}126.com.

Purpose: The interleukin-13 receptor 2 (IL-13R2) 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-13R2–specific CTLs.

Experimental Design: Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen (HLA)-A2/pIL-13R2_345-354 tetrameric complexes, anti-CD28 antibody, and CD83 molecules to cell-sized latex beads, and used to stimulate IL-13R2–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- production, and CTL reactivity.

Results: Tetramer staining assay showed that the induced CTLs specifically bound HLA-A2/pIL-13R2_345-354 tetramers. The CTLs specifically produced IFN- in response to the HLA-A2/pIL-13R2_345-354-aAPCs and exhibited specific lysis against T2 cells pulsed with the peptide pIL-13R2_345-354 and HLA-A2⁺ glioma cells expressing IL-13R2_345-354, whereas HLA-A2^– glioma cell lines that express IL-13R2_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-13R2_345-354 peptide could be a potential target of specific immunotherapy for HLA-A2⁺ patients with malignant glioma.