HLA Tetramer–Based Artificial Antigen-Presenting Cells Efficiently Stimulate CTLs Specific for Malignant Glioma
X Jiang, X Lu, R Liu, F Zhang, H Zhao - Clinical cancer research, 2007 - AACR
X Jiang, X Lu, R Liu, F Zhang, H Zhao
Clinical cancer research, 2007•AACRPurpose: The interleukin-13 receptor α2 (IL-13Rα2) 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-13Rα2–specific CTLs. Experimental Design:
Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen
(HLA)-A2/pIL-13Rα2345-354 tetrameric complexes, anti-CD28 antibody, and CD83
molecules to cell-sized latex beads, and used to stimulate IL-13Rα2–specific CTLs from the …
epitope not otherwise detected within the central nervous system. Here, we report a novel
approach for targeting malignant glioma with IL-13Rα2–specific CTLs. Experimental Design:
Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen
(HLA)-A2/pIL-13Rα2345-354 tetrameric complexes, anti-CD28 antibody, and CD83
molecules to cell-sized latex beads, and used to stimulate IL-13Rα2–specific CTLs from the …
Abstract
Purpose: The interleukin-13 receptor α2 (IL-13Rα2) 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-13Rα2–specific CTLs.
Experimental Design: Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen (HLA)-A2/pIL-13Rα2345-354 tetrameric complexes, anti-CD28 antibody, and CD83 molecules to cell-sized latex beads, and used to stimulate IL-13Rα2–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-γ production, and CTL reactivity.
Results: Tetramer staining assay showed that the induced CTLs specifically bound HLA-A2/pIL-13Rα2345-354 tetramers. The CTLs specifically produced IFN-γ in response to the HLA-A2/pIL-13Rα2345-354-aAPCs and exhibited specific lysis against T2 cells pulsed with the peptide pIL-13Rα2345-354 and HLA-A2+ glioma cells expressing IL-13Rα2345-354, whereas HLA-A2− glioma cell lines that express IL-13Rα2345-354 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-13Rα2345-354 peptide could be a potential target of specific immunotherapy for HLA-A2+ patients with malignant glioma.
AACR
