PMID- 18094414 OWN - NLM STAT- MEDLINE DCOM- 20080304 LR - 20231213 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 13 IP - 24 DP - 2007 Dec 15 TI - HLA Tetramer Based Artificial Antigen-Presenting Cells Efficiently Stimulate CTLs Specific for Malignant Glioma. PG - 7329-34 AB - 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. FAU - Jiang, Xiaobing AU - Jiang X AD - Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. jxb917@126.com FAU - Lu, Xiaoling AU - Lu X FAU - Liu, Ruen AU - Liu R FAU - Zhang, Fangcheng AU - Zhang F FAU - Zhao, Hongyang AU - Zhao H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antigens, CD) RN - 0 (CD28 Antigens) RN - 0 (HLA Antigens) RN - 0 (Immunoglobulins) RN - 0 (Interleukin-13 Receptor alpha2 Subunit) RN - 0 (Membrane Glycoproteins) SB - IM MH - Antigen-Presenting Cells/*immunology MH - Antigens, CD/immunology MH - Brain Neoplasms/*immunology MH - CD28 Antigens/immunology MH - Cells, Cultured MH - Coculture Techniques MH - Gene Expression MH - Glioma/*immunology MH - HLA Antigens/*immunology MH - Humans MH - Immunoglobulins/immunology MH - Interleukin-13 Receptor alpha2 Subunit/immunology MH - Lymphocyte Activation/immunology MH - Membrane Glycoproteins/immunology MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocytes, Cytotoxic/*immunology MH - CD83 Antigen EDAT- 2007/12/21 09:00 MHDA- 2008/03/05 09:00 CRDT- 2007/12/21 09:00 PHST- 2007/12/21 09:00 [pubmed] PHST- 2008/03/05 09:00 [medline] PHST- 2007/12/21 09:00 [entrez] AID - 13/24/7329 [pii] AID - 10.1158/1078-0432.CCR-07-1025 [doi] PST - ppublish SO - Clin Cancer Res. 2007 Dec 15;13(24):7329-34. doi: 10.1158/1078-0432.CCR-07-1025.