Generation of allo-restricted cytotoxic T lymphocytes against malignant glioma by artificial antigen-presenting cells.
The interleukin (IL) 13 receptor alpha2 (IL-13Ralpha2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. This study reported a novel approach for targeting malignant glioma with IL-13Ralpha2-specific allo-restricted cytotoxic T cells (CTLs) induced from the peripheral blood lymphocytes (PBLs) of HLA-A2-negative healthy donors by multiple stimulations with artificial antigen-presenting cells (aAPCs) made by coating HLA-A2/pIL-13Ralpha2(345-354) tetrameric complexes, anti-CD28 antibody and CD83 molecules to cell-sized latex beads. The induced allo-restricted CTLs exhibited specific lysis against T2 cells pulsed with the peptide pIL-13Ralpha2(345-354) and HLA-A2+ glioma cells expressing IL-13Ralpha2(345-354), while HLA-A2- glioma cell lines that express IL-13Ralpha2(345-354) could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-HLA class I monoclonal antibody. These results suggested the induced allo-restricted CTLs specific for IL-13Ralpha2(345-354) peptide could be a potential target of specific immunotherapy for HLA-A2+ patients with malignant glioma.
Lu
Xiao-Ling
XL
Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Jiang
Xiao-Bing
XB
Liu
Ru-En
RE
Zhang
Fang-Cheng
FC
Zhao
Hong-Yang
HY
D000938:Antigen-Presenting Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005910:Glioma / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000939:Epitopes; D015789:HLA-A2 Antigen; D053663:Interleukin-13 Receptor alpha2 Subunit; D010446:Peptide Fragments